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39 * \brief Implementation of the Weighted Histogram Analysis Method (WHAM)
41 * \author Jochen Hub <jhub@gwdg.de>
57 #include "gromacs/commandline/pargs.h"
58 #include "gromacs/fileio/tpxio.h"
59 #include "gromacs/fileio/xvgr.h"
60 #include "gromacs/gmxana/gmx_ana.h"
61 #include "gromacs/math/functions.h"
62 #include "gromacs/math/units.h"
63 #include "gromacs/math/vec.h"
64 #include "gromacs/mdtypes/inputrec.h"
65 #include "gromacs/mdtypes/md_enums.h"
66 #include "gromacs/mdtypes/pull-params.h"
67 #include "gromacs/mdtypes/state.h"
68 #include "gromacs/pulling/pull.h"
69 #include "gromacs/random/tabulatednormaldistribution.h"
70 #include "gromacs/random/threefry.h"
71 #include "gromacs/random/uniformintdistribution.h"
72 #include "gromacs/random/uniformrealdistribution.h"
73 #include "gromacs/utility/arraysize.h"
74 #include "gromacs/utility/cstringutil.h"
75 #include "gromacs/utility/exceptions.h"
76 #include "gromacs/utility/fatalerror.h"
77 #include "gromacs/utility/futil.h"
78 #include "gromacs/utility/gmxomp.h"
79 #include "gromacs/utility/pleasecite.h"
80 #include "gromacs/utility/smalloc.h"
82 //! longest file names allowed in input files
83 #define WHAM_MAXFILELEN 2048
86 * enum for energy units
89 enSel, en_kJ, en_kCal, en_kT, enNr
92 * enum for type of input files (pdos, tpr, or pullf)
95 whamin_unknown, whamin_tpr, whamin_pullxf, whamin_pdo
98 /*! \brief enum for bootstrapping method
100 * These bootstrap methods are supported:
101 * - bootstrap complete histograms with continuous weights (Bayesian bootstrap)
102 * (bsMethod_BayesianHist)
103 * - bootstrap complete histograms (bsMethod_hist)
104 * - bootstrap trajectories from given umbrella histograms. This generates new
105 * "synthetic" histograms (bsMethod_traj)
106 * - bootstrap trajectories from Gaussian with mu/sigma computed from
107 * the respective histogram (bsMethod_trajGauss). This gives very similar
108 * results compared to bsMethod_traj.
110 * ********************************************************************
111 * FOR MORE DETAILS ON THE BOOTSTRAP METHODS (INCLUDING EXAMPLES), SEE
112 * JS Hub, BL de Groot, D van der Spoel
113 * g_wham - A free weighted histogram analysis implementation including
114 * robust error and autocorrelation estimates,
115 * J Chem Theory Comput, 6(12), 3713-3720 (2010)
116 * ********************************************************************
119 bsMethod_unknown, bsMethod_BayesianHist, bsMethod_hist,
120 bsMethod_traj, bsMethod_trajGauss
123 //! Parameters of one pull coodinate
126 int pull_type; //!< such as constraint, umbrella, ...
127 int geometry; //!< such as distance, direction, cylinder
128 int ngroup; //!< the number of pull groups involved
129 ivec dim; //!< pull dimension with geometry distance
130 int ndim; //!< nr of pull_dim != 0
131 real k; //!< force constants in tpr file
132 real init_dist; //!< reference displacement
133 char coord_unit[256]; //!< unit of the displacement
136 //! Parameters of the umbrella potentials
140 * \name Using umbrella pull code since gromacs 4.x
143 int npullcrds; //!< nr of umbrella pull coordinates for reading
144 t_pullcoord *pcrd; //!< the pull coordinates
145 gmx_bool bPrintCOM; //!< COMs of pull groups writtn in pullx.xvg
146 gmx_bool bPrintRefValue; //!< Reference value for the coordinate written in pullx.xvg
147 gmx_bool bPrintComp; //!< Components of pull distance written to pullx.xvg ?
151 * \name Using PDO files common until gromacs 3.x
159 char PullName[4][256];
161 double UmbCons[4][3];
165 //! Data in the umbrella histograms
168 int nPull; //!< nr of pull groups in this pdo or pullf/x file
169 double **Histo; //!< nPull histograms
170 double **cum; //!< nPull cumulative distribution functions
171 int nBin; //!< nr of bins. identical to opt->bins
172 double *k; //!< force constants for the nPull coords
173 double *pos; //!< umbrella positions for the nPull coords
174 double *z; //!< z=(-Fi/kT) for the nPull coords. These values are iteratively computed during wham
175 int *N; //!< nr of data points in nPull histograms.
176 int *Ntot; //!< also nr of data points. N and Ntot only differ if bHistEq==TRUE
178 /*! \brief g = 1 + 2*tau[int]/dt where tau is the integrated autocorrelation time.
180 * Compare, e.g. Ferrenberg/Swendsen, PRL 63:1195 (1989),
181 * Kumar et al, J Comp Chem 13, 1011-1021 (1992), eq. 28
184 double *tau; //!< intetrated autocorrelation time (IACT)
185 double *tausmooth; //!< smoothed IACT
187 double dt; //!< timestep in the input data. Can be adapted with gmx wham option -dt
189 /*! \brief TRUE, if any data point of the histogram is within min and max, otherwise FALSE */
191 real **ztime; //!< input data z(t) as a function of time. Required to compute ACTs
193 /*! \brief average force estimated from average displacement, fAv=dzAv*k
195 * Used for integration to guess the potential.
198 real *aver; //!< average of histograms
199 real *sigma; //!< stddev of histograms
200 double *bsWeight; //!< for bootstrapping complete histograms with continuous weights
203 //! Selection of pull coordinates to be used in WHAM (one structure for each tpr file)
206 int n; //!< total nr of pull coords in this tpr file
207 int nUse; //!< nr of pull coords used
208 gmx_bool *bUse; //!< boolean array of size n. =1 if used, =0 if not
211 //! Parameters of WHAM
218 const char *fnTpr, *fnPullf, *fnCoordSel;
219 const char *fnPdo, *fnPullx; //!< file names of input
220 gmx_bool bTpr, bPullf, bPdo, bPullx; //!< input file types given?
221 real tmin, tmax, dt; //!< only read input within tmin and tmax with dt
223 gmx_bool bInitPotByIntegration; //!< before WHAM, guess potential by force integration. Yields 1.5 to 2 times faster convergence
224 int stepUpdateContrib; //!< update contribution table every ... iterations. Accelerates WHAM.
225 int nCoordsel; //!< if >0: use only certain group in WHAM, if ==0: use all groups
226 t_coordselection *coordsel; //!< for each tpr file: which pull coordinates to use in WHAM?
229 * \name Basic WHAM options
232 int bins; //!< nr of bins, min, max, and dz of profile
234 real Temperature, Tolerance; //!< temperature, converged when probability changes less than Tolerance
235 gmx_bool bCycl; //!< generate cyclic (periodic) PMF
238 * \name Output control
241 gmx_bool bLog; //!< energy output (instead of probability) for profile
242 int unit; //!< unit for PMF output kJ/mol or kT or kCal/mol
243 gmx_bool bSym; //!< symmetrize PMF around z=0 after WHAM, useful for membranes etc.
244 /*! \brief after wham, set prof to zero at this z-position.
245 * When bootstrapping, set zProf0 to a "stable" reference position.
248 gmx_bool bProf0Set; //!< setting profile to 0 at zProf0?
250 gmx_bool bBoundsOnly, bHistOnly; //!< determine min and max, or write histograms and exit
251 gmx_bool bAuto; //!< determine min and max automatically but do not exit
253 gmx_bool verbose; //!< more noisy wham mode
254 int stepchange; //!< print maximum change in prof after how many interations
255 gmx_output_env_t *oenv; //!< xvgr options
258 * \name Autocorrelation stuff
261 gmx_bool bTauIntGiven, bCalcTauInt; //!< IACT given or should be calculated?
262 real sigSmoothIact; //!< sigma of Gaussian to smooth ACTs
263 gmx_bool bAllowReduceIact; //!< Allow to reduce ACTs during smoothing. Otherwise ACT are only increased during smoothing
264 real acTrestart; //!< when computing ACT, time between restarting points
266 /* \brief Enforce the same weight for each umbella window, that is
267 * calculate with the same number of data points for
268 * each window. That can be reasonable, if the histograms
269 * have different length, but due to autocorrelation,
270 * a longer simulation should not have larger weightin wham.
276 * \name Bootstrapping stuff
279 int nBootStrap; //!< nr of bootstraps (50 is usually enough)
281 /* \brief bootstrap method
283 * if == bsMethod_hist, consider complete histograms as independent
284 * data points and, hence, only mix complete histograms.
285 * if == bsMethod_BayesianHist, consider complete histograms
286 * as independent data points, but assign random weights
287 * to the histograms during the bootstrapping ("Bayesian bootstrap")
288 * In case of long correlations (e.g., inside a channel), these
289 * will yield a more realistic error.
290 * if == bsMethod_traj(Gauss), generate synthetic histograms
292 * histogram by generating an autocorrelated random sequence
293 * that is distributed according to the respective given
294 * histogram. With bsMethod_trajGauss, bootstrap from a Gaussian
295 * (instead of from the umbrella histogram) to generate a new
300 /* \brief autocorrelation time (ACT) used to generate synthetic histograms. If ==0, use calculated ACF */
303 /* \brief when mixing histograms, mix only histograms withing blocks
304 long the reaction coordinate xi. Avoids gaps along xi. */
305 int histBootStrapBlockLength;
307 int bsSeed; //!< random seed for bootstrapping
309 /* \brief Write cumulative distribution functions (CDFs) of histograms
310 and write the generated histograms for each bootstrap */
314 * \name tabulated umbrella potential stuff
318 double *tabX, *tabY, tabMin, tabMax, tabDz;
321 gmx::DefaultRandomEngine rng; //!< gromacs random number generator
322 gmx::TabulatedNormalDistribution<> normalDistribution; //!< Uses default: real output, 14-bit table
325 //! Make an umbrella window (may contain several histograms)
326 static t_UmbrellaWindow * initUmbrellaWindows(int nwin)
328 t_UmbrellaWindow *win;
331 for (i = 0; i < nwin; i++)
333 win[i].Histo = win[i].cum = nullptr;
334 win[i].k = win[i].pos = win[i].z = nullptr;
335 win[i].N = win[i].Ntot = nullptr;
336 win[i].g = win[i].tau = win[i].tausmooth = nullptr;
337 win[i].bContrib = nullptr;
338 win[i].ztime = nullptr;
339 win[i].forceAv = nullptr;
340 win[i].aver = win[i].sigma = nullptr;
341 win[i].bsWeight = nullptr;
346 //! Delete an umbrella window (may contain several histograms)
347 static void freeUmbrellaWindows(t_UmbrellaWindow *win, int nwin)
350 for (i = 0; i < nwin; i++)
354 for (j = 0; j < win[i].nPull; j++)
356 sfree(win[i].Histo[j]);
361 for (j = 0; j < win[i].nPull; j++)
363 sfree(win[i].cum[j]);
368 for (j = 0; j < win[i].nPull; j++)
370 sfree(win[i].bContrib[j]);
382 sfree(win[i].tausmooth);
383 sfree(win[i].bContrib);
385 sfree(win[i].forceAv);
388 sfree(win[i].bsWeight);
394 * Read and setup tabulated umbrella potential
396 static void setup_tab(const char *fn, t_UmbrellaOptions *opt)
401 printf("Setting up tabulated potential from file %s\n", fn);
402 nl = read_xvg(fn, &y, &ny);
406 gmx_fatal(FARGS, "Found %d columns in %s. Expected 2.\n", ny, fn);
408 opt->tabMin = y[0][0];
409 opt->tabMax = y[0][nl-1];
410 opt->tabDz = (opt->tabMax-opt->tabMin)/(nl-1);
413 gmx_fatal(FARGS, "The tabulated potential in %s must be provided in \n"
414 "ascending z-direction", fn);
416 for (i = 0; i < nl-1; i++)
418 if (std::abs(y[0][i+1]-y[0][i]-opt->tabDz) > opt->tabDz/1e6)
420 gmx_fatal(FARGS, "z-values in %s are not equally spaced.\n", ny, fn);
425 for (i = 0; i < nl; i++)
427 opt->tabX[i] = y[0][i];
428 opt->tabY[i] = y[1][i];
430 printf("Found equally spaced tabulated potential from %g to %g, spacing %g\n",
431 opt->tabMin, opt->tabMax, opt->tabDz);
434 //! Read the header of an PDO file (position, force const, nr of groups)
435 static void read_pdo_header(FILE * file, t_UmbrellaHeader * header, t_UmbrellaOptions *opt)
438 char Buffer0[256], Buffer1[256], Buffer2[256], Buffer3[256], Buffer4[256];
440 std::istringstream ist;
443 if (fgets(line, 2048, file) == nullptr)
445 gmx_fatal(FARGS, "Error reading header from pdo file\n");
448 ist >> Buffer0 >> Buffer1 >> Buffer2;
449 if (std::strcmp(Buffer1, "UMBRELLA") != 0)
451 gmx_fatal(FARGS, "This does not appear to be a valid pdo file. Found %s, expected %s\n"
452 "(Found in first line: `%s')\n",
453 Buffer1, "UMBRELLA", line);
455 if (std::strcmp(Buffer2, "3.0") != 0)
457 gmx_fatal(FARGS, "This does not appear to be a version 3.0 pdo file");
461 if (fgets(line, 2048, file) == nullptr)
463 gmx_fatal(FARGS, "Error reading header from pdo file\n");
466 ist >> Buffer0 >> Buffer1 >> Buffer2 >> header->Dims[0] >> header->Dims[1] >> header->Dims[2];
467 /* printf("%d %d %d\n", header->Dims[0],header->Dims[1],header->Dims[2]); */
469 header->nDim = header->Dims[0] + header->Dims[1] + header->Dims[2];
470 if (header->nDim != 1)
472 gmx_fatal(FARGS, "Currently only supports one dimension");
476 if (fgets(line, 2048, file) == nullptr)
478 gmx_fatal(FARGS, "Error reading header from pdo file\n");
481 ist >> Buffer0 >> Buffer1 >> header->nSkip;
484 if (fgets(line, 2048, file) == nullptr)
486 gmx_fatal(FARGS, "Error reading header from pdo file\n");
489 ist >> Buffer0 >> Buffer1 >> Buffer2 >> header->Reference;
492 if (fgets(line, 2048, file) == nullptr)
494 gmx_fatal(FARGS, "Error reading header from pdo file\n");
497 ist >> Buffer0 >> Buffer1 >> Buffer2 >> Buffer3 >> Buffer4 >> header->nPull;
501 printf("\tFound nPull=%d , nSkip=%d, ref=%s\n", header->nPull, header->nSkip,
505 for (i = 0; i < header->nPull; ++i)
507 if (fgets(line, 2048, file) == nullptr)
509 gmx_fatal(FARGS, "Error reading header from pdo file\n");
512 ist >> Buffer0 >> Buffer1 >> Buffer2 >> header->PullName[i];
513 ist >> Buffer0 >> Buffer1 >> header->UmbPos[i][0];
514 ist >> Buffer0 >> Buffer1 >> header->UmbCons[i][0];
518 printf("\tpullgroup %d, pullname = %s, UmbPos = %g, UmbConst = %g\n",
519 i, header->PullName[i], header->UmbPos[i][0], header->UmbCons[i][0]);
523 if (fgets(line, 2048, file) == nullptr)
525 gmx_fatal(FARGS, "Cannot read from file\n");
529 if (std::strcmp(Buffer3, "#####") != 0)
531 gmx_fatal(FARGS, "Expected '#####', found %s. Hick.\n", Buffer3);
536 static char *fgets3(FILE *fp, char ptr[], int *len)
541 if (fgets(ptr, *len-1, fp) == nullptr)
546 while ((std::strchr(ptr, '\n') == nullptr) && (!feof(fp)))
548 /* This line is longer than len characters, let's increase len! */
552 if (fgets(p-1, STRLEN, fp) == nullptr)
557 slen = std::strlen(ptr);
558 if (ptr[slen-1] == '\n')
566 /*! \brief Read the data columns of and PDO file.
568 * TO DO: Get rid of the scanf function to avoid the clang warning.
569 * At the moment, this warning is avoided by hiding the format string
570 * the variable fmtlf.
572 static void read_pdo_data(FILE * file, t_UmbrellaHeader * header,
573 int fileno, t_UmbrellaWindow * win,
574 t_UmbrellaOptions *opt,
575 gmx_bool bGetMinMax, real *mintmp, real *maxtmp)
577 int i, inttemp, bins, count, ntot;
578 real minval, maxval, minfound = 1e20, maxfound = -1e20;
579 double temp, time, time0 = 0, dt;
581 t_UmbrellaWindow * window = nullptr;
582 gmx_bool timeok, dt_ok = 1;
583 char *tmpbuf = nullptr, fmt[256], fmtign[256], fmtlf[5] = "%lf";
584 int len = STRLEN, dstep = 1;
585 const int blocklen = 4096;
586 int *lennow = nullptr;
595 /* Need to alocate memory and set up structure */
596 window->nPull = header->nPull;
599 snew(window->Histo, window->nPull);
600 snew(window->z, window->nPull);
601 snew(window->k, window->nPull);
602 snew(window->pos, window->nPull);
603 snew(window->N, window->nPull);
604 snew(window->Ntot, window->nPull);
605 snew(window->g, window->nPull);
606 snew(window->bsWeight, window->nPull);
608 window->bContrib = nullptr;
610 if (opt->bCalcTauInt)
612 snew(window->ztime, window->nPull);
616 window->ztime = nullptr;
618 snew(lennow, window->nPull);
620 for (i = 0; i < window->nPull; ++i)
623 window->bsWeight[i] = 1.;
624 snew(window->Histo[i], bins);
625 window->k[i] = header->UmbCons[i][0];
626 window->pos[i] = header->UmbPos[i][0];
630 if (opt->bCalcTauInt)
632 window->ztime[i] = nullptr;
636 /* Done with setup */
642 minval = maxval = bins = 0; /* Get rid of warnings */
647 while ( (ptr = fgets3(file, tmpbuf, &len)) != nullptr)
651 if (ptr[0] == '#' || std::strlen(ptr) < 2)
656 /* Initiate format string */
658 std::strcat(fmtign, "%*s");
660 sscanf(ptr, fmtlf, &time); /* printf("Time %f\n",time); */
661 /* Round time to fs */
662 time = 1.0/1000*( static_cast<gmx_int64_t> (time*1000+0.5) );
664 /* get time step of pdo file */
674 dstep = static_cast<int>(opt->dt/dt+0.5);
682 window->dt = dt*dstep;
687 dt_ok = ((count-1)%dstep == 0);
688 timeok = (dt_ok && time >= opt->tmin && time <= opt->tmax);
690 printf(" time = %f, (tmin,tmax)=(%e,%e), dt_ok=%d timeok=%d\n",
691 time,opt->tmin, opt->tmax, dt_ok,timeok); */
695 for (i = 0; i < header->nPull; ++i)
697 std::strcpy(fmt, fmtign);
698 std::strcat(fmt, "%lf"); /* Creating a format stings such as "%*s...%*s%lf" */
699 std::strcat(fmtign, "%*s"); /* ignoring one more entry in the next loop */
700 if (sscanf(ptr, fmt, &temp))
702 temp += header->UmbPos[i][0];
716 if (opt->bCalcTauInt)
718 /* save time series for autocorrelation analysis */
719 ntot = window->Ntot[i];
720 if (ntot >= lennow[i])
722 lennow[i] += blocklen;
723 srenew(window->ztime[i], lennow[i]);
725 window->ztime[i][ntot] = temp;
729 temp /= (maxval-minval);
731 temp = std::floor(temp);
733 inttemp = static_cast<int> (temp);
740 else if (inttemp >= bins)
746 if (inttemp >= 0 && inttemp < bins)
748 window->Histo[i][inttemp] += 1.;
756 if (time > opt->tmax)
760 printf("time %f larger than tmax %f, stop reading pdo file\n", time, opt->tmax);
776 /*! \brief Set identical weights for all histograms
778 * Normally, the weight is given by the number data points in each
779 * histogram, together with the autocorrelation time. This can be overwritten
780 * by this routine (not recommended). Since we now support autocorrelations, it is better to set
781 * an appropriate autocorrelation times instead of using this function.
783 static void enforceEqualWeights(t_UmbrellaWindow * window, int nWindows)
785 int i, k, j, NEnforced;
788 NEnforced = window[0].Ntot[0];
789 printf("\nFound -hist-eq. Enforcing equal weights for all histograms, \ni.e. doing a "
790 "non-weighted histogram analysis method. Ndata = %d\n", NEnforced);
791 /* enforce all histograms to have the same weight as the very first histogram */
793 for (j = 0; j < nWindows; ++j)
795 for (k = 0; k < window[j].nPull; ++k)
797 ratio = 1.0*NEnforced/window[j].Ntot[k];
798 for (i = 0; i < window[0].nBin; ++i)
800 window[j].Histo[k][i] *= ratio;
802 window[j].N[k] = static_cast<int>(ratio*window[j].N[k] + 0.5);
807 /*! \brief Simple linear interpolation between two given tabulated points
809 static double tabulated_pot(double dist, t_UmbrellaOptions *opt)
812 double pl, pu, dz, dp;
814 jl = static_cast<int> (std::floor((dist-opt->tabMin)/opt->tabDz));
816 if (jl < 0 || ju >= opt->tabNbins)
818 gmx_fatal(FARGS, "Distance %f out of bounds of tabulated potential (jl=%d, ju=%d).\n"
819 "Provide an extended table.", dist, jl, ju);
823 dz = dist-opt->tabX[jl];
824 dp = (pu-pl)*dz/opt->tabDz;
830 * Check which bins substiantially contribute (accelerates WHAM)
832 * Don't worry, that routine does not mean we compute the PMF in limited precision.
833 * After rapid convergence (using only substiantal contributions), we always switch to
836 static void setup_acc_wham(double *profile, t_UmbrellaWindow * window, int nWindows,
837 t_UmbrellaOptions *opt)
839 int i, j, k, nGrptot = 0, nContrib = 0, nTot = 0;
840 double U, min = opt->min, dz = opt->dz, temp, ztot_half, distance, ztot, contrib1, contrib2;
841 gmx_bool bAnyContrib;
842 static int bFirst = 1;
843 static double wham_contrib_lim;
847 for (i = 0; i < nWindows; ++i)
849 nGrptot += window[i].nPull;
851 wham_contrib_lim = opt->Tolerance/nGrptot;
854 ztot = opt->max-opt->min;
857 for (i = 0; i < nWindows; ++i)
859 if (!window[i].bContrib)
861 snew(window[i].bContrib, window[i].nPull);
863 for (j = 0; j < window[i].nPull; ++j)
865 if (!window[i].bContrib[j])
867 snew(window[i].bContrib[j], opt->bins);
870 for (k = 0; k < opt->bins; ++k)
872 temp = (1.0*k+0.5)*dz+min;
873 distance = temp - window[i].pos[j]; /* distance to umbrella center */
875 { /* in cyclic wham: */
876 if (distance > ztot_half) /* |distance| < ztot_half */
880 else if (distance < -ztot_half)
885 /* Note: there are two contributions to bin k in the wham equations:
886 i) N[j]*exp(- U/(BOLTZ*opt->Temperature) + window[i].z[j])
887 ii) exp(- U/(BOLTZ*opt->Temperature))
888 where U is the umbrella potential
889 If any of these number is larger wham_contrib_lim, I set contrib=TRUE
894 U = 0.5*window[i].k[j]*gmx::square(distance); /* harmonic potential assumed. */
898 U = tabulated_pot(distance, opt); /* Use tabulated potential */
900 contrib1 = profile[k]*std::exp(-U/(BOLTZ*opt->Temperature));
901 contrib2 = window[i].N[j]*std::exp(-U/(BOLTZ*opt->Temperature) + window[i].z[j]);
902 window[i].bContrib[j][k] = (contrib1 > wham_contrib_lim || contrib2 > wham_contrib_lim);
903 bAnyContrib = (bAnyContrib | window[i].bContrib[j][k]);
904 if (window[i].bContrib[j][k])
910 /* If this histo is far outside min and max all bContrib may be FALSE,
911 causing a floating point exception later on. To avoid that, switch
915 for (k = 0; k < opt->bins; ++k)
917 window[i].bContrib[j][k] = TRUE;
924 printf("Initialized rapid wham stuff (contrib tolerance %g)\n"
925 "Evaluating only %d of %d expressions.\n\n", wham_contrib_lim, nContrib, nTot);
930 printf("Updated rapid wham stuff. (evaluating only %d of %d contributions)\n",
936 //! Compute the PMF (one of the two main WHAM routines)
937 static void calc_profile(double *profile, t_UmbrellaWindow * window, int nWindows,
938 t_UmbrellaOptions *opt, gmx_bool bExact)
940 double ztot_half, ztot, min = opt->min, dz = opt->dz;
942 ztot = opt->max-opt->min;
949 int nthreads = gmx_omp_get_max_threads();
950 int thread_id = gmx_omp_get_thread_num();
952 int i0 = thread_id*opt->bins/nthreads;
953 int i1 = std::min(opt->bins, ((thread_id+1)*opt->bins)/nthreads);
955 for (i = i0; i < i1; ++i)
958 double num, denom, invg, temp = 0, distance, U = 0;
960 for (j = 0; j < nWindows; ++j)
962 for (k = 0; k < window[j].nPull; ++k)
964 invg = 1.0/window[j].g[k] * window[j].bsWeight[k];
965 temp = (1.0*i+0.5)*dz+min;
966 num += invg*window[j].Histo[k][i];
968 if (!(bExact || window[j].bContrib[k][i]))
972 distance = temp - window[j].pos[k]; /* distance to umbrella center */
974 { /* in cyclic wham: */
975 if (distance > ztot_half) /* |distance| < ztot_half */
979 else if (distance < -ztot_half)
987 U = 0.5*window[j].k[k]*gmx::square(distance); /* harmonic potential assumed. */
991 U = tabulated_pot(distance, opt); /* Use tabulated potential */
993 denom += invg*window[j].N[k]*std::exp(-U/(BOLTZ*opt->Temperature) + window[j].z[k]);
996 profile[i] = num/denom;
999 GMX_CATCH_ALL_AND_EXIT_WITH_FATAL_ERROR;
1003 //! Compute the free energy offsets z (one of the two main WHAM routines)
1004 static double calc_z(double * profile, t_UmbrellaWindow * window, int nWindows,
1005 t_UmbrellaOptions *opt, gmx_bool bExact)
1007 double min = opt->min, dz = opt->dz, ztot_half, ztot;
1008 double maxglob = -1e20;
1010 ztot = opt->max-opt->min;
1013 #pragma omp parallel
1017 int nthreads = gmx_omp_get_max_threads();
1018 int thread_id = gmx_omp_get_thread_num();
1020 int i0 = thread_id*nWindows/nthreads;
1021 int i1 = std::min(nWindows, ((thread_id+1)*nWindows)/nthreads);
1022 double maxloc = -1e20;
1024 for (i = i0; i < i1; ++i)
1026 double total = 0, temp, distance, U = 0;
1029 for (j = 0; j < window[i].nPull; ++j)
1032 for (k = 0; k < window[i].nBin; ++k)
1034 if (!(bExact || window[i].bContrib[j][k]))
1038 temp = (1.0*k+0.5)*dz+min;
1039 distance = temp - window[i].pos[j]; /* distance to umbrella center */
1041 { /* in cyclic wham: */
1042 if (distance > ztot_half) /* |distance| < ztot_half */
1046 else if (distance < -ztot_half)
1054 U = 0.5*window[i].k[j]*gmx::square(distance); /* harmonic potential assumed. */
1058 U = tabulated_pot(distance, opt); /* Use tabulated potential */
1060 total += profile[k]*std::exp(-U/(BOLTZ*opt->Temperature));
1062 /* Avoid floating point exception if window is far outside min and max */
1065 total = -std::log(total);
1071 temp = std::abs(total - window[i].z[j]);
1076 window[i].z[j] = total;
1079 /* Now get maximum maxloc from the threads and put in maxglob */
1080 if (maxloc > maxglob)
1082 #pragma omp critical
1084 if (maxloc > maxglob)
1091 GMX_CATCH_ALL_AND_EXIT_WITH_FATAL_ERROR;
1097 //! Make PMF symmetric around 0 (useful e.g. for membranes)
1098 static void symmetrizeProfile(double* profile, t_UmbrellaOptions *opt)
1100 int i, j, bins = opt->bins;
1101 double *prof2, min = opt->min, max = opt->max, dz = opt->dz, zsym, deltaz, profsym;
1104 if (min > 0. || max < 0.)
1106 gmx_fatal(FARGS, "Cannot symmetrize profile around z=0 with min=%f and max=%f\n",
1107 opt->min, opt->max);
1112 for (i = 0; i < bins; i++)
1116 /* bin left of zsym */
1117 j = static_cast<int> (std::floor((zsym-min)/dz-0.5));
1118 if (j >= 0 && (j+1) < bins)
1120 /* interpolate profile linearly between bins j and j+1 */
1121 z1 = min+(j+0.5)*dz;
1123 profsym = profile[j] + (profile[j+1]-profile[j])/dz*deltaz;
1124 /* average between left and right */
1125 prof2[i] = 0.5*(profsym+profile[i]);
1129 prof2[i] = profile[i];
1133 std::memcpy(profile, prof2, bins*sizeof(double));
1137 //! Set energy unit (kJ/mol,kT,kCal/mol) and set it to zero at opt->zProf0
1138 static void prof_normalization_and_unit(double * profile, t_UmbrellaOptions *opt)
1141 double unit_factor = 1., diff;
1145 /* Not log? Nothing to do! */
1151 /* Get profile in units of kT, kJ/mol, or kCal/mol */
1152 if (opt->unit == en_kT)
1156 else if (opt->unit == en_kJ)
1158 unit_factor = BOLTZ*opt->Temperature;
1160 else if (opt->unit == en_kCal)
1162 unit_factor = (BOLTZ/CAL2JOULE)*opt->Temperature;
1166 gmx_fatal(FARGS, "Sorry, I don't know this energy unit.");
1169 for (i = 0; i < bins; i++)
1171 if (profile[i] > 0.0)
1173 profile[i] = -std::log(profile[i])*unit_factor;
1177 /* shift to zero at z=opt->zProf0 */
1178 if (!opt->bProf0Set)
1184 /* Get bin with shortest distance to opt->zProf0
1185 (-0.5 from bin position and +0.5 from rounding cancel) */
1186 imin = static_cast<int>((opt->zProf0-opt->min)/opt->dz);
1191 else if (imin >= bins)
1195 diff = profile[imin];
1199 for (i = 0; i < bins; i++)
1205 //! Make an array of random integers (used for bootstrapping)
1206 static void getRandomIntArray(int nPull, int blockLength, int* randomArray, gmx::DefaultRandomEngine * rng)
1208 gmx::UniformIntDistribution<int> dist(0, blockLength-1);
1210 int ipull, blockBase, nr, ipullRandom;
1212 if (blockLength == 0)
1214 blockLength = nPull;
1217 for (ipull = 0; ipull < nPull; ipull++)
1219 blockBase = (ipull/blockLength)*blockLength;
1221 { /* make sure nothing bad happens in the last block */
1222 nr = dist(*rng); // [0,blockLength-1]
1223 ipullRandom = blockBase + nr;
1225 while (ipullRandom >= nPull);
1226 if (ipullRandom < 0 || ipullRandom >= nPull)
1228 gmx_fatal(FARGS, "Ups, random iWin = %d, nPull = %d, nr = %d, "
1229 "blockLength = %d, blockBase = %d\n",
1230 ipullRandom, nPull, nr, blockLength, blockBase);
1232 randomArray[ipull] = ipullRandom;
1234 /*for (ipull=0; ipull<nPull; ipull++)
1235 printf("%d ",randomArray[ipull]); printf("\n"); */
1238 /*! \brief Set pull group information of a synthetic histogram
1240 * This is used when bootstapping new trajectories and thereby create new histogtrams,
1241 * but it is not required if we bootstrap complete histograms.
1243 static void copy_pullgrp_to_synthwindow(t_UmbrellaWindow *synthWindow,
1244 t_UmbrellaWindow *thisWindow, int pullid)
1246 synthWindow->N [0] = thisWindow->N [pullid];
1247 synthWindow->Histo [0] = thisWindow->Histo [pullid];
1248 synthWindow->pos [0] = thisWindow->pos [pullid];
1249 synthWindow->z [0] = thisWindow->z [pullid];
1250 synthWindow->k [0] = thisWindow->k [pullid];
1251 synthWindow->bContrib[0] = thisWindow->bContrib [pullid];
1252 synthWindow->g [0] = thisWindow->g [pullid];
1253 synthWindow->bsWeight[0] = thisWindow->bsWeight [pullid];
1256 /*! \brief Calculate cumulative distribution function of of all histograms.
1258 * This allow to create random number sequences
1259 * which are distributed according to the histograms. Required to generate
1260 * the "synthetic" histograms for the Bootstrap method
1262 static void calc_cumulatives(t_UmbrellaWindow *window, int nWindows,
1263 t_UmbrellaOptions *opt, const char *fnhist, const char *xlabel)
1267 char *fn = nullptr, *buf = nullptr;
1270 if (opt->bs_verbose)
1272 snew(fn, std::strlen(fnhist)+10);
1273 snew(buf, std::strlen(fnhist)+10);
1274 sprintf(fn, "%s_cumul.xvg", std::strncpy(buf, fnhist, std::strlen(fnhist)-4));
1275 fp = xvgropen(fn, "CDFs of umbrella windows", xlabel, "CDF", opt->oenv);
1279 for (i = 0; i < nWindows; i++)
1281 snew(window[i].cum, window[i].nPull);
1282 for (j = 0; j < window[i].nPull; j++)
1284 snew(window[i].cum[j], nbin+1);
1285 window[i].cum[j][0] = 0.;
1286 for (k = 1; k <= nbin; k++)
1288 window[i].cum[j][k] = window[i].cum[j][k-1]+window[i].Histo[j][k-1];
1291 /* normalize CDFs. Ensure cum[nbin]==1 */
1292 last = window[i].cum[j][nbin];
1293 for (k = 0; k <= nbin; k++)
1295 window[i].cum[j][k] /= last;
1300 printf("Cumulative distribution functions of all histograms created.\n");
1301 if (opt->bs_verbose)
1303 for (k = 0; k <= nbin; k++)
1305 fprintf(fp, "%g\t", opt->min+k*opt->dz);
1306 for (i = 0; i < nWindows; i++)
1308 for (j = 0; j < window[i].nPull; j++)
1310 fprintf(fp, "%g\t", window[i].cum[j][k]);
1315 printf("Wrote cumulative distribution functions to %s\n", fn);
1323 /*! \brief Return j such that xx[j] <= x < xx[j+1]
1325 * This is used to generate a random sequence distributed according to a histogram
1327 static void searchCumulative(double xx[], int n, double x, int *j)
1349 else if (x == xx[n-1])
1359 //! Bootstrap new trajectories and thereby generate new (bootstrapped) histograms
1360 static void create_synthetic_histo(t_UmbrellaWindow *synthWindow, t_UmbrellaWindow *thisWindow,
1361 int pullid, t_UmbrellaOptions *opt)
1363 int N, i, nbins, r_index, ibin;
1364 double r, tausteps = 0.0, a, ap, dt, x, invsqrt2, g, y, sig = 0., z, mu = 0.;
1367 N = thisWindow->N[pullid];
1368 dt = thisWindow->dt;
1369 nbins = thisWindow->nBin;
1371 /* tau = autocorrelation time */
1372 if (opt->tauBootStrap > 0.0)
1374 tausteps = opt->tauBootStrap/dt;
1376 else if (opt->bTauIntGiven || opt->bCalcTauInt)
1378 /* calc tausteps from g=1+2tausteps */
1379 g = thisWindow->g[pullid];
1385 "When generating hypothetical trajectories from given umbrella histograms,\n"
1386 "autocorrelation times (ACTs) are required. Otherwise the statistical error\n"
1387 "cannot be predicted. You have 3 options:\n"
1388 "1) Make gmx wham estimate the ACTs (options -ac and -acsig).\n"
1389 "2) Calculate the ACTs by yourself (e.g. with g_analyze) and provide them\n");
1391 " with option -iiact for all umbrella windows.\n"
1392 "3) If all ACTs are identical and know, you can define them with -bs-tau.\n"
1393 " Use option (3) only if you are sure what you're doing, you may severely\n"
1394 " underestimate the error if a too small ACT is given.\n");
1395 gmx_fatal(FARGS, errstr);
1398 synthWindow->N [0] = N;
1399 synthWindow->pos [0] = thisWindow->pos[pullid];
1400 synthWindow->z [0] = thisWindow->z[pullid];
1401 synthWindow->k [0] = thisWindow->k[pullid];
1402 synthWindow->bContrib[0] = thisWindow->bContrib[pullid];
1403 synthWindow->g [0] = thisWindow->g [pullid];
1404 synthWindow->bsWeight[0] = thisWindow->bsWeight[pullid];
1406 for (i = 0; i < nbins; i++)
1408 synthWindow->Histo[0][i] = 0.;
1411 if (opt->bsMethod == bsMethod_trajGauss)
1413 sig = thisWindow->sigma [pullid];
1414 mu = thisWindow->aver [pullid];
1417 /* Genrate autocorrelated Gaussian random variable with autocorrelation time tau
1419 If x and y are random numbers from N(0,1) (Gaussian with average 0 and sigma=1),
1421 z = a*x + sqrt(1-a^2)*y
1422 is also from N(0,1), and cov(z,x) = a. Thus, by gerenating a sequence
1423 x' = a*x + sqrt(1-a^2)*y, the sequnce x(t) is from N(0,1) and has an autocorrelation
1425 C(t) = exp(-t/tau) with tau=-1/ln(a)
1427 Then, use error function to turn the Gaussian random variable into a uniformly
1428 distributed one in [0,1]. Eventually, use cumulative distribution function of
1429 histogram to get random variables distributed according to histogram.
1430 Note: The ACT of the flat distribution and of the generated histogram is not
1431 100% exactly tau, but near tau (my test was 3.8 instead of 4).
1433 a = std::exp(-1.0/tausteps);
1434 ap = std::sqrt(1.0-a*a);
1435 invsqrt2 = 1.0/std::sqrt(2.0);
1437 /* init random sequence */
1438 x = opt->normalDistribution(opt->rng);
1440 if (opt->bsMethod == bsMethod_traj)
1442 /* bootstrap points from the umbrella histograms */
1443 for (i = 0; i < N; i++)
1445 y = opt->normalDistribution(opt->rng);
1447 /* get flat distribution in [0,1] using cumulative distribution function of Gauusian
1448 Note: CDF(Gaussian) = 0.5*{1+erf[x/sqrt(2)]}
1450 r = 0.5*(1+std::erf(x*invsqrt2));
1451 searchCumulative(thisWindow->cum[pullid], nbins+1, r, &r_index);
1452 synthWindow->Histo[0][r_index] += 1.;
1455 else if (opt->bsMethod == bsMethod_trajGauss)
1457 /* bootstrap points from a Gaussian with the same average and sigma
1458 as the respective umbrella histogram. The idea was, that -given
1459 limited sampling- the bootstrapped histograms are otherwise biased
1460 from the limited sampling of the US histos. However, bootstrapping from
1461 the Gaussian seems to yield a similar estimate. */
1465 y = opt->normalDistribution(opt->rng);
1468 ibin = static_cast<int> (std::floor((z-opt->min)/opt->dz));
1473 while ( (ibin += nbins) < 0)
1478 else if (ibin >= nbins)
1480 while ( (ibin -= nbins) >= nbins)
1487 if (ibin >= 0 && ibin < nbins)
1489 synthWindow->Histo[0][ibin] += 1.;
1496 gmx_fatal(FARGS, "Unknown bsMethod (id %d). That should not happen.\n", opt->bsMethod);
1500 /*! \brief Write all histograms to a file
1502 * If bs_index>=0, a number is added to the output file name to allow the ouput of all
1503 * sets of bootstrapped histograms.
1505 static void print_histograms(const char *fnhist, t_UmbrellaWindow * window, int nWindows,
1506 int bs_index, t_UmbrellaOptions *opt, const char *xlabel)
1508 char *fn = nullptr, *buf = nullptr, title[256];
1514 snew(fn, std::strlen(fnhist)+10);
1515 snew(buf, std::strlen(fnhist)+1);
1516 sprintf(fn, "%s_bs%d.xvg", std::strncpy(buf, fnhist, std::strlen(fnhist)-4), bs_index);
1517 sprintf(title, "Umbrella histograms. Bootstrap #%d", bs_index);
1521 fn = gmx_strdup(fnhist);
1522 std::strcpy(title, "Umbrella histograms");
1525 fp = xvgropen(fn, title, xlabel, "count", opt->oenv);
1528 /* Write histograms */
1529 for (l = 0; l < bins; ++l)
1531 fprintf(fp, "%e\t", (l+0.5)*opt->dz+opt->min);
1532 for (i = 0; i < nWindows; ++i)
1534 for (j = 0; j < window[i].nPull; ++j)
1536 fprintf(fp, "%e\t", window[i].Histo[j][l]);
1543 printf("Wrote %s\n", fn);
1551 //! Used for qsort to sort random numbers
1552 static int func_wham_is_larger(const void *a, const void *b)
1571 //! Make random weights for histograms for the Bayesian bootstrap of complete histograms)
1572 static void setRandomBsWeights(t_UmbrellaWindow *synthwin, int nAllPull, t_UmbrellaOptions *opt)
1576 gmx::UniformRealDistribution<real> dist(0, nAllPull);
1580 /* generate ordered random numbers between 0 and nAllPull */
1581 for (i = 0; i < nAllPull-1; i++)
1583 r[i] = dist(opt->rng);
1585 qsort((void *)r, nAllPull-1, sizeof(double), &func_wham_is_larger);
1586 r[nAllPull-1] = 1.0*nAllPull;
1588 synthwin[0].bsWeight[0] = r[0];
1589 for (i = 1; i < nAllPull; i++)
1591 synthwin[i].bsWeight[0] = r[i]-r[i-1];
1594 /* avoid to have zero weight by adding a tiny value */
1595 for (i = 0; i < nAllPull; i++)
1597 if (synthwin[i].bsWeight[0] < 1e-5)
1599 synthwin[i].bsWeight[0] = 1e-5;
1606 //! The main bootstrapping routine
1607 static void do_bootstrapping(const char *fnres, const char* fnprof, const char *fnhist,
1608 const char *xlabel, char* ylabel, double *profile,
1609 t_UmbrellaWindow * window, int nWindows, t_UmbrellaOptions *opt)
1611 t_UmbrellaWindow * synthWindow;
1612 double *bsProfile, *bsProfiles_av, *bsProfiles_av2, maxchange = 1e20, tmp, stddev;
1613 int i, j, *randomArray = nullptr, winid, pullid, ib;
1614 int iAllPull, nAllPull, *allPull_winId, *allPull_pullId;
1616 gmx_bool bExact = FALSE;
1618 /* init random generator */
1619 if (opt->bsSeed == 0)
1621 opt->bsSeed = static_cast<int>(gmx::makeRandomSeed());
1623 opt->rng.seed(opt->bsSeed);
1625 snew(bsProfile, opt->bins);
1626 snew(bsProfiles_av, opt->bins);
1627 snew(bsProfiles_av2, opt->bins);
1629 /* Create array of all pull groups. Note that different windows
1630 may have different nr of pull groups
1631 First: Get total nr of pull groups */
1633 for (i = 0; i < nWindows; i++)
1635 nAllPull += window[i].nPull;
1637 snew(allPull_winId, nAllPull);
1638 snew(allPull_pullId, nAllPull);
1640 /* Setup one array of all pull groups */
1641 for (i = 0; i < nWindows; i++)
1643 for (j = 0; j < window[i].nPull; j++)
1645 allPull_winId[iAllPull] = i;
1646 allPull_pullId[iAllPull] = j;
1651 /* setup stuff for synthetic windows */
1652 snew(synthWindow, nAllPull);
1653 for (i = 0; i < nAllPull; i++)
1655 synthWindow[i].nPull = 1;
1656 synthWindow[i].nBin = opt->bins;
1657 snew(synthWindow[i].Histo, 1);
1658 if (opt->bsMethod == bsMethod_traj || opt->bsMethod == bsMethod_trajGauss)
1660 snew(synthWindow[i].Histo[0], opt->bins);
1662 snew(synthWindow[i].N, 1);
1663 snew(synthWindow[i].pos, 1);
1664 snew(synthWindow[i].z, 1);
1665 snew(synthWindow[i].k, 1);
1666 snew(synthWindow[i].bContrib, 1);
1667 snew(synthWindow[i].g, 1);
1668 snew(synthWindow[i].bsWeight, 1);
1671 switch (opt->bsMethod)
1674 snew(randomArray, nAllPull);
1675 printf("\n\nWhen computing statistical errors by bootstrapping entire histograms:\n");
1676 please_cite(stdout, "Hub2006");
1678 case bsMethod_BayesianHist:
1679 /* just copy all histogams into synthWindow array */
1680 for (i = 0; i < nAllPull; i++)
1682 winid = allPull_winId [i];
1683 pullid = allPull_pullId[i];
1684 copy_pullgrp_to_synthwindow(synthWindow+i, window+winid, pullid);
1688 case bsMethod_trajGauss:
1689 calc_cumulatives(window, nWindows, opt, fnhist, xlabel);
1692 gmx_fatal(FARGS, "Unknown bootstrap method. That should not have happened.\n");
1695 /* do bootstrapping */
1696 fp = xvgropen(fnprof, "Bootstrap profiles", xlabel, ylabel, opt->oenv);
1697 for (ib = 0; ib < opt->nBootStrap; ib++)
1699 printf(" *******************************************\n"
1700 " ******** Start bootstrap nr %d ************\n"
1701 " *******************************************\n", ib+1);
1703 switch (opt->bsMethod)
1706 /* bootstrap complete histograms from given histograms */
1707 getRandomIntArray(nAllPull, opt->histBootStrapBlockLength, randomArray, &opt->rng);
1708 for (i = 0; i < nAllPull; i++)
1710 winid = allPull_winId [randomArray[i]];
1711 pullid = allPull_pullId[randomArray[i]];
1712 copy_pullgrp_to_synthwindow(synthWindow+i, window+winid, pullid);
1715 case bsMethod_BayesianHist:
1716 /* keep histos, but assign random weights ("Bayesian bootstrap") */
1717 setRandomBsWeights(synthWindow, nAllPull, opt);
1720 case bsMethod_trajGauss:
1721 /* create new histos from given histos, that is generate new hypothetical
1723 for (i = 0; i < nAllPull; i++)
1725 winid = allPull_winId[i];
1726 pullid = allPull_pullId[i];
1727 create_synthetic_histo(synthWindow+i, window+winid, pullid, opt);
1732 /* write histos in case of verbose output */
1733 if (opt->bs_verbose)
1735 print_histograms(fnhist, synthWindow, nAllPull, ib, opt, xlabel);
1742 std::memcpy(bsProfile, profile, opt->bins*sizeof(double)); /* use profile as guess */
1745 if ( (i%opt->stepUpdateContrib) == 0)
1747 setup_acc_wham(bsProfile, synthWindow, nAllPull, opt);
1749 if (maxchange < opt->Tolerance)
1753 if (((i%opt->stepchange) == 0 || i == 1) && i != 0)
1755 printf("\t%4d) Maximum change %e\n", i, maxchange);
1757 calc_profile(bsProfile, synthWindow, nAllPull, opt, bExact);
1760 while ( (maxchange = calc_z(bsProfile, synthWindow, nAllPull, opt, bExact)) > opt->Tolerance || !bExact);
1761 printf("\tConverged in %d iterations. Final maximum change %g\n", i, maxchange);
1765 prof_normalization_and_unit(bsProfile, opt);
1768 /* symmetrize profile around z=0 */
1771 symmetrizeProfile(bsProfile, opt);
1774 /* save stuff to get average and stddev */
1775 for (i = 0; i < opt->bins; i++)
1778 bsProfiles_av[i] += tmp;
1779 bsProfiles_av2[i] += tmp*tmp;
1780 fprintf(fp, "%e\t%e\n", (i+0.5)*opt->dz+opt->min, tmp);
1782 fprintf(fp, "%s\n", output_env_get_print_xvgr_codes(opt->oenv) ? "&" : "");
1786 /* write average and stddev */
1787 fp = xvgropen(fnres, "Average and stddev from bootstrapping", xlabel, ylabel, opt->oenv);
1788 if (output_env_get_print_xvgr_codes(opt->oenv))
1790 fprintf(fp, "@TYPE xydy\n");
1792 for (i = 0; i < opt->bins; i++)
1794 bsProfiles_av [i] /= opt->nBootStrap;
1795 bsProfiles_av2[i] /= opt->nBootStrap;
1796 tmp = bsProfiles_av2[i]-gmx::square(bsProfiles_av[i]);
1797 stddev = (tmp >= 0.) ? std::sqrt(tmp) : 0.; /* Catch rouding errors */
1798 fprintf(fp, "%e\t%e\t%e\n", (i+0.5)*opt->dz+opt->min, bsProfiles_av [i], stddev);
1801 printf("Wrote boot strap result to %s\n", fnres);
1804 //! Return type of input file based on file extension (xvg, pdo, or tpr)
1805 static int whaminFileType(char *fn)
1808 len = std::strlen(fn);
1809 if (std::strcmp(fn+len-3, "tpr") == 0)
1813 else if (std::strcmp(fn+len-3, "xvg") == 0 || std::strcmp(fn+len-6, "xvg.gz") == 0)
1815 return whamin_pullxf;
1817 else if (std::strcmp(fn+len-3, "pdo") == 0 || std::strcmp(fn+len-6, "pdo.gz") == 0)
1823 gmx_fatal(FARGS, "Unknown file type of %s. Should be tpr, xvg, or pdo.\n", fn);
1825 return whamin_unknown;
1828 //! Read the files names in pdo-files.dat, pullf/x-files.dat, tpr-files.dat
1829 static void read_wham_in(const char *fn, char ***filenamesRet, int *nfilesRet,
1830 t_UmbrellaOptions *opt)
1832 char **filename = nullptr, tmp[WHAM_MAXFILELEN+2];
1833 int nread, sizenow, i, block = 1;
1836 fp = gmx_ffopen(fn, "r");
1839 while (fgets(tmp, sizeof(tmp), fp) != nullptr)
1841 if (std::strlen(tmp) >= WHAM_MAXFILELEN)
1843 gmx_fatal(FARGS, "Filename too long in %s. Only %d characters allowed.\n", fn, WHAM_MAXFILELEN);
1845 if (nread >= sizenow)
1848 srenew(filename, sizenow);
1849 for (i = sizenow-block; i < sizenow; i++)
1851 snew(filename[i], WHAM_MAXFILELEN);
1854 /* remove newline if there is one */
1855 if (tmp[std::strlen(tmp)-1] == '\n')
1857 tmp[std::strlen(tmp)-1] = '\0';
1859 std::strcpy(filename[nread], tmp);
1862 printf("Found file %s in %s\n", filename[nread], fn);
1866 *filenamesRet = filename;
1870 //! Open a file or a pipe to a gzipped file
1871 static FILE *open_pdo_pipe(const char *fn, t_UmbrellaOptions *opt, gmx_bool *bPipeOpen)
1873 char Buffer[1024], gunzip[1024], *Path = nullptr;
1874 FILE *pipe = nullptr;
1875 static gmx_bool bFirst = 1;
1877 /* gzipped pdo file? */
1878 if ((std::strcmp(fn+std::strlen(fn)-3, ".gz") == 0))
1880 /* search gunzip executable */
1881 if (!(Path = getenv("GMX_PATH_GZIP")))
1883 if (gmx_fexist("/bin/gunzip"))
1885 sprintf(gunzip, "%s", "/bin/gunzip");
1887 else if (gmx_fexist("/usr/bin/gunzip"))
1889 sprintf(gunzip, "%s", "/usr/bin/gunzip");
1893 gmx_fatal(FARGS, "Cannot find executable gunzip in /bin or /usr/bin.\n"
1894 "You may want to define the path to gunzip "
1895 "with the environment variable GMX_PATH_GZIP.", gunzip);
1900 sprintf(gunzip, "%s/gunzip", Path);
1901 if (!gmx_fexist(gunzip))
1903 gmx_fatal(FARGS, "Cannot find executable %s. Please define the path to gunzip"
1904 " in the environmental varialbe GMX_PATH_GZIP.", gunzip);
1909 printf("Using gunzip executable %s\n", gunzip);
1912 if (!gmx_fexist(fn))
1914 gmx_fatal(FARGS, "File %s does not exist.\n", fn);
1916 sprintf(Buffer, "%s -c < %s", gunzip, fn);
1919 printf("Executing command '%s'\n", Buffer);
1922 if ((pipe = popen(Buffer, "r")) == nullptr)
1924 gmx_fatal(FARGS, "Unable to open pipe to `%s'\n", Buffer);
1927 gmx_fatal(FARGS, "Cannot open a compressed file on platform without pipe support");
1933 pipe = gmx_ffopen(fn, "r");
1940 //! Close file or pipe
1941 static void pdo_close_file(FILE *fp)
1950 //! Reading all pdo files
1951 static void read_pdo_files(char **fn, int nfiles, t_UmbrellaHeader* header,
1952 t_UmbrellaWindow *window, t_UmbrellaOptions *opt)
1955 real mintmp, maxtmp, done = 0.;
1958 /* char Buffer0[1000]; */
1962 gmx_fatal(FARGS, "No files found. Hick.");
1965 /* if min and max are not given, get min and max from the input files */
1968 printf("Automatic determination of boundaries from %d pdo files...\n", nfiles);
1971 for (i = 0; i < nfiles; ++i)
1973 file = open_pdo_pipe(fn[i], opt, &bPipeOpen);
1974 /*fgets(Buffer0,999,file);
1975 fprintf(stderr,"First line '%s'\n",Buffer0); */
1976 done = 100.0*(i+1)/nfiles;
1977 fprintf(stdout, "\rOpening %s ... [%2.0f%%]", fn[i], done); fflush(stdout);
1982 read_pdo_header(file, header, opt);
1983 /* here only determine min and max of this window */
1984 read_pdo_data(file, header, i, nullptr, opt, TRUE, &mintmp, &maxtmp);
1985 if (maxtmp > opt->max)
1989 if (mintmp < opt->min)
1995 pdo_close_file(file);
2003 printf("\nDetermined boundaries to %f and %f\n\n", opt->min, opt->max);
2004 if (opt->bBoundsOnly)
2006 printf("Found option -boundsonly, now exiting.\n");
2010 /* store stepsize in profile */
2011 opt->dz = (opt->max-opt->min)/opt->bins;
2013 /* Having min and max, we read in all files */
2014 /* Loop over all files */
2015 for (i = 0; i < nfiles; ++i)
2017 done = 100.0*(i+1)/nfiles;
2018 fprintf(stdout, "\rOpening %s ... [%2.0f%%]", fn[i], done); fflush(stdout);
2023 file = open_pdo_pipe(fn[i], opt, &bPipeOpen);
2024 read_pdo_header(file, header, opt);
2025 /* load data into window */
2026 read_pdo_data(file, header, i, window, opt, FALSE, nullptr, nullptr);
2027 if ((window+i)->Ntot[0] == 0)
2029 fprintf(stderr, "\nWARNING, no data points read from file %s (check -b option)\n", fn[i]);
2033 pdo_close_file(file);
2041 for (i = 0; i < nfiles; ++i)
2048 //! translate 0/1 to N/Y to write pull dimensions
2049 #define int2YN(a) (((a) == 0) ? ("N") : ("Y"))
2051 //! Read pull groups from a tpr file (including position, force const, geometry, number of groups)
2052 static void read_tpr_header(const char *fn, t_UmbrellaHeader* header, t_UmbrellaOptions *opt, t_coordselection *coordsel)
2054 t_inputrec irInstance;
2055 t_inputrec *ir = &irInstance;
2057 static int first = 1;
2059 /* printf("Reading %s \n",fn); */
2060 read_tpx_state(fn, ir, &state, nullptr);
2064 gmx_fatal(FARGS, "This is not a tpr with COM pulling");
2066 if (ir->pull->ncoord == 0)
2068 gmx_fatal(FARGS, "No pull coordinates found in %s", fn);
2071 /* Read overall pull info */
2072 header->npullcrds = ir->pull->ncoord;
2073 header->bPrintCOM = ir->pull->bPrintCOM;
2074 header->bPrintRefValue = ir->pull->bPrintRefValue;
2075 header->bPrintComp = ir->pull->bPrintComp;
2077 /* Read pull coordinates */
2078 snew(header->pcrd, header->npullcrds);
2079 for (int i = 0; i < ir->pull->ncoord; i++)
2081 header->pcrd[i].pull_type = ir->pull->coord[i].eType;
2082 header->pcrd[i].geometry = ir->pull->coord[i].eGeom;
2083 header->pcrd[i].ngroup = ir->pull->coord[i].ngroup;
2084 header->pcrd[i].k = ir->pull->coord[i].k;
2085 header->pcrd[i].init_dist = ir->pull->coord[i].init;
2087 copy_ivec(ir->pull->coord[i].dim, header->pcrd[i].dim);
2088 header->pcrd[i].ndim = header->pcrd[i].dim[XX] + header->pcrd[i].dim[YY] + header->pcrd[i].dim[ZZ];
2090 std::strcpy(header->pcrd[i].coord_unit,
2091 pull_coordinate_units(&ir->pull->coord[i]));
2093 if (ir->efep != efepNO && ir->pull->coord[i].k != ir->pull->coord[i].kB)
2095 gmx_fatal(FARGS, "Seems like you did free-energy perturbation, and you perturbed the force constant."
2096 " This is not supported.\n");
2098 if (coordsel && (coordsel->n != ir->pull->ncoord))
2100 gmx_fatal(FARGS, "Found %d pull coordinates in %s, but %d columns in the respective line\n"
2101 "coordinate selection file (option -is)\n", ir->pull->ncoord, fn, coordsel->n);
2105 /* Check pull coords for consistency */
2107 ivec thedim = { 0, 0, 0 };
2108 bool geometryIsSet = false;
2109 for (int i = 0; i < ir->pull->ncoord; i++)
2111 if (coordsel == nullptr || coordsel->bUse[i])
2113 if (header->pcrd[i].pull_type != epullUMBRELLA)
2115 gmx_fatal(FARGS, "%s: Pull coordinate %d is of type \"%s\", expected \"umbrella\". Only umbrella coodinates can enter WHAM.\n"
2116 "If you have umrella and non-umbrella coordinates, you can select the umbrella coordinates with gmx wham -is\n",
2117 fn, i+1, epull_names[header->pcrd[i].pull_type]);
2121 geom = header->pcrd[i].geometry;
2122 copy_ivec(header->pcrd[i].dim, thedim);
2123 geometryIsSet = true;
2125 if (geom != header->pcrd[i].geometry)
2127 gmx_fatal(FARGS, "%s: Your pull coordinates have different pull geometry (coordinate 1: %s, coordinate %d: %s)\n"
2128 "If you want to use only some pull coordinates in WHAM, please select them with option gmx wham -is\n",
2129 fn, epullg_names[geom], i+1, epullg_names[header->pcrd[i].geometry]);
2131 if (thedim[XX] != header->pcrd[i].dim[XX] || thedim[YY] != header->pcrd[i].dim[YY] || thedim[ZZ] != header->pcrd[i].dim[ZZ])
2133 gmx_fatal(FARGS, "%s: Your pull coordinates have different pull dimensions (coordinate 1: %s %s %s, coordinate %d: %s %s %s)\n"
2134 "If you want to use only some pull coordinates in WHAM, please select them with option gmx wham -is\n",
2135 fn, int2YN(thedim[XX]), int2YN(thedim[YY]), int2YN(thedim[ZZ]), i+1,
2136 int2YN(header->pcrd[i].dim[XX]), int2YN(header->pcrd[i].dim[YY]), int2YN(header->pcrd[i].dim[ZZ]));
2138 if (header->pcrd[i].geometry == epullgCYL)
2140 if (header->pcrd[i].dim[XX] || header->pcrd[i].dim[YY] || (!header->pcrd[i].dim[ZZ]))
2142 gmx_fatal(FARGS, "With pull geometry 'cylinder', expected pulling in Z direction only.\n"
2143 "However, found dimensions [%s %s %s]\n",
2144 int2YN(header->pcrd[i].dim[XX]), int2YN(header->pcrd[i].dim[YY]),
2145 int2YN(header->pcrd[i].dim[ZZ]));
2148 if (header->pcrd[i].k <= 0.0)
2150 gmx_fatal(FARGS, "%s: Pull coordinate %d has force constant of of %g in %s.\n"
2151 "That doesn't seem to be an Umbrella tpr.\n",
2152 fn, i+1, header->pcrd[i].k);
2157 if (opt->verbose || first)
2159 printf("\nFile %s, %d coordinates, with these options:\n", fn, header->npullcrds);
2161 for (int i = 0; i < ir->pull->ncoord; i++)
2163 int lentmp = strlen(epullg_names[header->pcrd[i].geometry]);
2164 maxlen = (lentmp > maxlen) ? lentmp : maxlen;
2167 sprintf(fmt, "\tGeometry %%-%ds k = %%-8g position = %%-8g dimensions [%%s %%s %%s] (%%d dimensions). Used: %%s\n",
2169 for (int i = 0; i < ir->pull->ncoord; i++)
2171 bool use = (coordsel == nullptr || coordsel->bUse[i]);
2173 epullg_names[header->pcrd[i].geometry], header->pcrd[i].k, header->pcrd[i].init_dist,
2174 int2YN(header->pcrd[i].dim[XX]), int2YN(header->pcrd[i].dim[YY]), int2YN(header->pcrd[i].dim[ZZ]),
2175 header->pcrd[i].ndim, use ? "Yes" : "No");
2176 printf("\tPull group coordinates of %d groups expected in pullx files.\n", ir->pull->bPrintCOM ? header->pcrd[i].ngroup : 0);
2178 printf("\tReference value of the coordinate%s expected in pullx files.\n",
2179 header->bPrintRefValue ? "" : " not");
2181 if (!opt->verbose && first)
2183 printf("\tUse option -v to see this output for all input tpr files\n\n");
2189 //! Read pullx.xvg or pullf.xvg
2190 static void read_pull_xf(const char *fn, t_UmbrellaHeader * header,
2191 t_UmbrellaWindow * window,
2192 t_UmbrellaOptions *opt,
2193 gmx_bool bGetMinMax, real *mintmp, real *maxtmp,
2194 t_coordselection *coordsel)
2196 double **y = nullptr, pos = 0., t, force, time0 = 0., dt;
2197 int ny, nt, bins, ibin, i, g, gUsed, dstep = 1;
2198 int nColExpect, ntot, column;
2199 real min, max, minfound = 1e20, maxfound = -1e20;
2200 gmx_bool dt_ok, timeok;
2201 const char *quantity;
2202 const int blocklen = 4096;
2203 int *lennow = nullptr;
2204 static gmx_bool bFirst = TRUE;
2207 * Data columns in pull output:
2208 * - in force output pullf.xvg:
2209 * No reference columns, one column per pull coordinate
2211 * - in position output pullx.xvg:
2212 * * optionally, ndim columns for COMs of all groups (depending on on mdp options pull-print-com);
2213 * * The displacement, always one column. Note: with pull-print-components = yes, the dx/dy/dz would
2214 * be written separately into pullx file, but this is not supported and throws an error below;
2215 * * optionally, the position of the reference coordinate (depending on pull-print-ref-value)
2218 if (header->bPrintComp && opt->bPullx)
2220 gmx_fatal(FARGS, "gmx wham cannot read pullx files if the components of the coordinate was written\n"
2221 "(mdp option pull-print-components). Provide the pull force files instead (with option -if).\n");
2224 int *nColThisCrd, *nColCOMCrd, *nColRefCrd;
2225 snew(nColThisCrd, header->npullcrds);
2226 snew(nColCOMCrd, header->npullcrds);
2227 snew(nColRefCrd, header->npullcrds);
2229 if (opt->bPullx == FALSE)
2231 /* pullf reading: simply one column per coordinate */
2232 for (g = 0; g < header->npullcrds; g++)
2241 /* pullx reading. Note explanation above. */
2242 for (g = 0; g < header->npullcrds; g++)
2244 nColRefCrd[g] = (header->bPrintRefValue ? 1 : 0);
2245 nColCOMCrd[g] = (header->bPrintCOM ? header->pcrd[g].ndim*header->pcrd[g].ngroup : 0);
2246 nColThisCrd[g] = 1 + nColCOMCrd[g] + nColRefCrd[g];
2250 nColExpect = 1; /* time column */
2251 for (g = 0; g < header->npullcrds; g++)
2253 nColExpect += nColThisCrd[g];
2256 /* read pullf or pullx. Could be optimized if min and max are given. */
2257 nt = read_xvg(fn, &y, &ny);
2259 /* Check consistency */
2260 quantity = opt->bPullx ? "position" : "force";
2263 gmx_fatal(FARGS, "Empty pull %s file %s\n", quantity, fn);
2265 if (bFirst || opt->verbose)
2267 printf("\nReading pull %s file %s, expecting %d columns:\n", quantity, fn, nColExpect);
2268 for (i = 0; i < header->npullcrds; i++)
2270 printf("\tColumns for pull coordinate %d\n", i+1);
2271 printf("\t\treaction coordinate: %d\n"
2272 "\t\tcenter-of-mass of groups: %d\n"
2273 "\t\treference position column: %s\n",
2274 1, nColCOMCrd[i], (header->bPrintRefValue ? "Yes" : "No"));
2276 printf("\tFound %d times in %s\n", nt, fn);
2279 if (nColExpect != ny)
2281 gmx_fatal(FARGS, "Expected %d columns (including time column) in %s, but found %d."
2282 " Maybe you confused options -if and -ix ?", nColExpect, fn, ny);
2293 window->dt = y[0][1]-y[0][0];
2295 else if (opt->nBootStrap && opt->tauBootStrap != 0.0)
2297 fprintf(stderr, "\n *** WARNING, Could not determine time step in %s\n", fn);
2300 /* Need to alocate memory and set up structure for windows */
2303 /* Use only groups selected with option -is file */
2304 if (header->npullcrds != coordsel->n)
2306 gmx_fatal(FARGS, "tpr file contains %d pull groups, but expected %d from group selection file\n",
2307 header->npullcrds, coordsel->n);
2309 window->nPull = coordsel->nUse;
2313 window->nPull = header->npullcrds;
2316 window->nBin = bins;
2317 snew(window->Histo, window->nPull);
2318 snew(window->z, window->nPull);
2319 snew(window->k, window->nPull);
2320 snew(window->pos, window->nPull);
2321 snew(window->N, window->nPull);
2322 snew(window->Ntot, window->nPull);
2323 snew(window->g, window->nPull);
2324 snew(window->bsWeight, window->nPull);
2325 window->bContrib = nullptr;
2327 if (opt->bCalcTauInt)
2329 snew(window->ztime, window->nPull);
2333 window->ztime = nullptr;
2335 snew(lennow, window->nPull);
2337 for (g = 0; g < window->nPull; ++g)
2340 window->bsWeight [g] = 1.;
2342 window->Ntot [g] = 0;
2344 snew(window->Histo[g], bins);
2346 if (opt->bCalcTauInt)
2348 window->ztime[g] = nullptr;
2352 /* Copying umbrella center and force const is more involved since not
2353 all pull groups from header (tpr file) may be used in window variable */
2354 for (g = 0, gUsed = 0; g < header->npullcrds; ++g)
2356 if (coordsel && (coordsel->bUse[g] == FALSE))
2360 window->k [gUsed] = header->pcrd[g].k;
2361 window->pos[gUsed] = header->pcrd[g].init_dist;
2366 { /* only determine min and max */
2369 min = max = bins = 0; /* Get rid of warnings */
2373 for (i = 0; i < nt; i++)
2375 /* Do you want that time frame? */
2376 t = 1.0/1000*( static_cast<gmx_int64_t> ((y[0][i]*1000) + 0.5)); /* round time to fs */
2378 /* get time step of pdo file and get dstep from opt->dt */
2388 dstep = static_cast<int>(opt->dt/dt+0.5);
2396 window->dt = dt*dstep;
2400 dt_ok = (i%dstep == 0);
2401 timeok = (dt_ok && t >= opt->tmin && t <= opt->tmax);
2403 printf(" time = %f, (tmin,tmax)=(%e,%e), dt_ok=%d timeok=%d\n",
2404 t,opt->tmin, opt->tmax, dt_ok,timeok); */
2407 /* Note: if coordsel == NULL:
2408 * all groups in pullf/x file are stored in this window, and gUsed == g
2409 * if coordsel != NULL:
2410 * only groups with coordsel.bUse[g]==TRUE are stored. gUsed is not always equal g
2413 for (g = 0; g < header->npullcrds; ++g)
2415 /* was this group selected for application in WHAM? */
2416 if (coordsel && (coordsel->bUse[g] == FALSE))
2424 /* y has 1 time column y[0] and one column per force y[1],...,y[nCrds] */
2426 pos = -force/header->pcrd[g].k + header->pcrd[g].init_dist;
2430 /* Pick the correct column index.
2431 Note that there is always exactly one displacement column.
2434 for (int j = 0; j < g; j++)
2436 column += nColThisCrd[j];
2441 /* printf("crd %d dpos %f poseq %f pos %f \n",g,dpos,poseq,pos); */
2455 if (gUsed >= window->nPull)
2457 gmx_fatal(FARGS, "gUsed too large (%d, nPull=%d). This error should have been caught before.\n",
2458 gUsed, window->nPull);
2461 if (opt->bCalcTauInt && !bGetMinMax)
2463 /* save time series for autocorrelation analysis */
2464 ntot = window->Ntot[gUsed];
2465 /* printf("i %d, ntot %d, lennow[g] = %d\n",i,ntot,lennow[g]); */
2466 if (ntot >= lennow[gUsed])
2468 lennow[gUsed] += blocklen;
2469 srenew(window->ztime[gUsed], lennow[gUsed]);
2471 window->ztime[gUsed][ntot] = pos;
2474 ibin = static_cast<int> (std::floor((pos-min)/(max-min)*bins));
2479 while ( (ibin += bins) < 0)
2484 else if (ibin >= bins)
2486 while ( (ibin -= bins) >= bins)
2492 if (ibin >= 0 && ibin < bins)
2494 window->Histo[gUsed][ibin] += 1.;
2497 window->Ntot[gUsed]++;
2501 else if (t > opt->tmax)
2505 printf("time %f larger than tmax %f, stop reading this pullx/pullf file\n", t, opt->tmax);
2517 for (i = 0; i < ny; i++)
2523 //! read pullf-files.dat or pullx-files.dat and tpr-files.dat
2524 static void read_tpr_pullxf_files(char **fnTprs, char **fnPull, int nfiles,
2525 t_UmbrellaHeader* header,
2526 t_UmbrellaWindow *window, t_UmbrellaOptions *opt)
2529 real mintmp, maxtmp;
2531 printf("Reading %d tpr and pullf files\n", nfiles);
2533 /* min and max not given? */
2536 printf("Automatic determination of boundaries...\n");
2539 for (i = 0; i < nfiles; i++)
2541 if (whaminFileType(fnTprs[i]) != whamin_tpr)
2543 gmx_fatal(FARGS, "Expected the %d'th file in input file to be a tpr file\n", i);
2545 read_tpr_header(fnTprs[i], header, opt, (opt->nCoordsel > 0) ? &opt->coordsel[i] : nullptr);
2546 if (whaminFileType(fnPull[i]) != whamin_pullxf)
2548 gmx_fatal(FARGS, "Expected the %d'th file in input file to be a xvg (pullx/pullf) file\n", i);
2550 read_pull_xf(fnPull[i], header, nullptr, opt, TRUE, &mintmp, &maxtmp,
2551 (opt->nCoordsel > 0) ? &opt->coordsel[i] : nullptr);
2552 if (maxtmp > opt->max)
2556 if (mintmp < opt->min)
2561 printf("\nDetermined boundaries to %f and %f\n\n", opt->min, opt->max);
2562 if (opt->bBoundsOnly)
2564 printf("Found option -boundsonly, now exiting.\n");
2568 /* store stepsize in profile */
2569 opt->dz = (opt->max-opt->min)/opt->bins;
2571 bool foundData = false;
2572 for (i = 0; i < nfiles; i++)
2574 if (whaminFileType(fnTprs[i]) != whamin_tpr)
2576 gmx_fatal(FARGS, "Expected the %d'th file in input file to be a tpr file\n", i);
2578 read_tpr_header(fnTprs[i], header, opt, (opt->nCoordsel > 0) ? &opt->coordsel[i] : nullptr);
2579 if (whaminFileType(fnPull[i]) != whamin_pullxf)
2581 gmx_fatal(FARGS, "Expected the %d'th file in input file to be a xvg (pullx/pullf) file\n", i);
2583 read_pull_xf(fnPull[i], header, window+i, opt, FALSE, nullptr, nullptr,
2584 (opt->nCoordsel > 0) ? &opt->coordsel[i] : nullptr);
2585 if (window[i].Ntot[0] == 0)
2587 fprintf(stderr, "\nWARNING, no data points read from file %s (check -b option)\n", fnPull[i]);
2596 gmx_fatal(FARGS, "No data points were found in pullf/pullx files. Maybe you need to specify the -b option?\n");
2599 for (i = 0; i < nfiles; i++)
2608 /*! \brief Read integrated autocorrelation times from input file (option -iiact)
2610 * Note: Here we consider tau[int] := int_0^inf ACF(t) as the integrated autocorrelation times.
2611 * The factor `g := 1 + 2*tau[int]` subsequently enters the uncertainty.
2613 static void readIntegratedAutocorrelationTimes(t_UmbrellaWindow *window, int nwins, const char* fn)
2615 int nlines, ny, i, ig;
2618 printf("Readging Integrated autocorrelation times from %s ...\n", fn);
2619 nlines = read_xvg(fn, &iact, &ny);
2620 if (nlines != nwins)
2622 gmx_fatal(FARGS, "Found %d lines with integrated autocorrelation times in %s.\nExpected %d",
2625 for (i = 0; i < nlines; i++)
2627 if (window[i].nPull != ny)
2629 gmx_fatal(FARGS, "You are providing autocorrelation times with option -iiact and the\n"
2630 "number of pull groups is different in different simulations. That is not\n"
2631 "supported yet. Sorry.\n");
2633 for (ig = 0; ig < window[i].nPull; ig++)
2635 /* compare Kumar et al, J Comp Chem 13, 1011-1021 (1992) */
2636 window[i].g[ig] = 1+2*iact[ig][i]/window[i].dt;
2638 if (iact[ig][i] <= 0.0)
2640 fprintf(stderr, "\nWARNING, IACT = %f (window %d, group %d)\n", iact[ig][i], i, ig);
2647 /*! \brief Smooth autocorreltion times along the reaction coordinate.
2650 * if the ACT is subject to high uncertainty in case if limited sampling. Note
2651 * that -in case of limited sampling- the ACT may be severely underestimated.
2652 * Note: the g=1+2tau are overwritten.
2653 * If opt->bAllowReduceIact==FALSE, the ACTs are never reduced, only increased
2656 static void smoothIact(t_UmbrellaWindow *window, int nwins, t_UmbrellaOptions *opt)
2659 double pos, dpos2, siglim, siglim2, gaufact, invtwosig2, w, weight, tausm;
2661 /* only evaluate within +- 3sigma of the Gausian */
2662 siglim = 3.0*opt->sigSmoothIact;
2663 siglim2 = gmx::square(siglim);
2664 /* pre-factor of Gaussian */
2665 gaufact = 1.0/(std::sqrt(2*M_PI)*opt->sigSmoothIact);
2666 invtwosig2 = 0.5/gmx::square(opt->sigSmoothIact);
2668 for (i = 0; i < nwins; i++)
2670 snew(window[i].tausmooth, window[i].nPull);
2671 for (ig = 0; ig < window[i].nPull; ig++)
2675 pos = window[i].pos[ig];
2676 for (j = 0; j < nwins; j++)
2678 for (jg = 0; jg < window[j].nPull; jg++)
2680 dpos2 = gmx::square(window[j].pos[jg]-pos);
2681 if (dpos2 < siglim2)
2683 w = gaufact*std::exp(-dpos2*invtwosig2);
2685 tausm += w*window[j].tau[jg];
2686 /*printf("Weight %g dpos2=%g pos=%g gaufact=%g invtwosig2=%g\n",
2687 w,dpos2,pos,gaufact,invtwosig2); */
2692 if (opt->bAllowReduceIact || tausm > window[i].tau[ig])
2694 window[i].tausmooth[ig] = tausm;
2698 window[i].tausmooth[ig] = window[i].tau[ig];
2700 window[i].g[ig] = 1+2*tausm/window[i].dt;
2705 //! Stop integrating autoccorelation function when ACF drops under this value
2706 #define WHAM_AC_ZERO_LIMIT 0.05
2708 /*! \brief Try to compute the autocorrelation time for each umbrealla window
2710 static void calcIntegratedAutocorrelationTimes(t_UmbrellaWindow *window, int nwins,
2711 t_UmbrellaOptions *opt, const char *fn, const char *xlabel)
2713 int i, ig, ncorr, ntot, j, k, *count, restart;
2714 real *corr, c0, dt, tmp;
2715 real *ztime, av, tausteps;
2716 FILE *fp, *fpcorr = nullptr;
2720 fpcorr = xvgropen("hist_autocorr.xvg", "Autocorrelation functions of umbrella windows",
2721 "time [ps]", "autocorrelation function", opt->oenv);
2725 for (i = 0; i < nwins; i++)
2727 fprintf(stdout, "\rEstimating integrated autocorrelation times ... [%2.0f%%] ...", 100.*(i+1)/nwins);
2729 ntot = window[i].Ntot[0];
2731 /* using half the maximum time as length of autocorrelation function */
2735 gmx_fatal(FARGS, "Tryig to estimtate autocorrelation time from only %d"
2736 " points. Provide more pull data!", ntot);
2739 /* snew(corrSq,ncorr); */
2742 snew(window[i].tau, window[i].nPull);
2743 restart = static_cast<int>(opt->acTrestart/dt+0.5);
2749 for (ig = 0; ig < window[i].nPull; ig++)
2751 if (ntot != window[i].Ntot[ig])
2753 gmx_fatal(FARGS, "Encountered different nr of frames in different pull groups.\n"
2754 "That should not happen. (%d and %d)\n", ntot, window[i].Ntot[ig]);
2756 ztime = window[i].ztime[ig];
2758 /* calc autocorrelation function C(t) = < [z(tau)-<z>]*[z(tau+t)-<z>]> */
2759 for (j = 0, av = 0; (j < ntot); j++)
2764 for (k = 0; (k < ncorr); k++)
2769 for (j = 0; (j < ntot); j += restart)
2771 for (k = 0; (k < ncorr) && (j+k < ntot); k++)
2773 tmp = (ztime[j]-av)*(ztime[j+k]-av);
2775 /* corrSq[k] += tmp*tmp; */
2779 /* divide by nr of frames for each time displacement */
2780 for (k = 0; (k < ncorr); k++)
2782 /* count probably = (ncorr-k+(restart-1))/restart; */
2783 corr[k] = corr[k]/count[k];
2784 /* variance of autocorrelation function */
2785 /* corrSq[k]=corrSq[k]/count[k]; */
2787 /* normalize such that corr[0] == 0 */
2789 for (k = 0; (k < ncorr); k++)
2792 /* corrSq[k]*=c0*c0; */
2795 /* write ACFs in verbose mode */
2798 for (k = 0; (k < ncorr); k++)
2800 fprintf(fpcorr, "%g %g\n", k*dt, corr[k]);
2802 fprintf(fpcorr, "%s\n", output_env_get_print_xvgr_codes(opt->oenv) ? "&" : "");
2805 /* esimate integrated correlation time, fitting is too unstable */
2806 tausteps = 0.5*corr[0];
2807 /* consider corr below WHAM_AC_ZERO_LIMIT as noise */
2808 for (j = 1; (j < ncorr) && (corr[j] > WHAM_AC_ZERO_LIMIT); j++)
2810 tausteps += corr[j];
2813 /* g = 1+2*tau, see. Ferrenberg/Swendsen, PRL 63:1195 (1989) or
2814 Kumar et al, eq. 28 ff. */
2815 window[i].tau[ig] = tausteps*dt;
2816 window[i].g[ig] = 1+2*tausteps;
2817 /* printf("win %d, group %d, estimated correlation time = %g ps\n",i,ig,window[i].tau[ig]); */
2828 /* plot IACT along reaction coordinate */
2829 fp = xvgropen(fn, "Integrated autocorrelation times", xlabel, "IACT [ps]", opt->oenv);
2830 if (output_env_get_print_xvgr_codes(opt->oenv))
2832 fprintf(fp, "@ s0 symbol 1\n@ s0 symbol size 0.5\n@ s0 line linestyle 0\n");
2833 fprintf(fp, "# WIN tau(gr1) tau(gr2) ...\n");
2834 for (i = 0; i < nwins; i++)
2836 fprintf(fp, "# %3d ", i);
2837 for (ig = 0; ig < window[i].nPull; ig++)
2839 fprintf(fp, " %11g", window[i].tau[ig]);
2844 for (i = 0; i < nwins; i++)
2846 for (ig = 0; ig < window[i].nPull; ig++)
2848 fprintf(fp, "%8g %8g\n", window[i].pos[ig], window[i].tau[ig]);
2851 if (opt->sigSmoothIact > 0.0)
2853 printf("Smoothing autocorrelation times along reaction coordinate with Gaussian of sig = %g\n",
2854 opt->sigSmoothIact);
2855 /* smooth IACT along reaction coordinate and overwrite g=1+2tau */
2856 smoothIact(window, nwins, opt);
2857 fprintf(fp, "%s\n", output_env_get_print_xvgr_codes(opt->oenv) ? "&" : "");
2858 if (output_env_get_print_xvgr_codes(opt->oenv))
2860 fprintf(fp, "@ s1 symbol 1\n@ s1 symbol size 0.5\n@ s1 line linestyle 0\n");
2861 fprintf(fp, "@ s1 symbol color 2\n");
2863 for (i = 0; i < nwins; i++)
2865 for (ig = 0; ig < window[i].nPull; ig++)
2867 fprintf(fp, "%8g %8g\n", window[i].pos[ig], window[i].tausmooth[ig]);
2872 printf("Wrote %s\n", fn);
2876 * compute average and sigma of each umbrella histogram
2878 static void averageSigma(t_UmbrellaWindow *window, int nwins)
2881 real av, sum2, sig, diff, *ztime, nSamplesIndep;
2883 for (i = 0; i < nwins; i++)
2885 snew(window[i].aver, window[i].nPull);
2886 snew(window[i].sigma, window[i].nPull);
2888 ntot = window[i].Ntot[0];
2889 for (ig = 0; ig < window[i].nPull; ig++)
2891 ztime = window[i].ztime[ig];
2892 for (k = 0, av = 0.; k < ntot; k++)
2897 for (k = 0, sum2 = 0.; k < ntot; k++)
2902 sig = std::sqrt(sum2/ntot);
2903 window[i].aver[ig] = av;
2905 /* Note: This estimate for sigma is biased from the limited sampling.
2906 Correct sigma by n/(n-1) where n = number of independent
2907 samples. Only possible if IACT is known.
2911 nSamplesIndep = window[i].N[ig]/(window[i].tau[ig]/window[i].dt);
2912 window[i].sigma[ig] = sig * nSamplesIndep/(nSamplesIndep-1);
2916 window[i].sigma[ig] = sig;
2918 printf("win %d, aver = %f sig = %f\n", i, av, window[i].sigma[ig]);
2925 * Use histograms to compute average force on pull group.
2927 static void computeAverageForce(t_UmbrellaWindow *window, int nWindows, t_UmbrellaOptions *opt)
2929 int i, j, bins = opt->bins, k;
2930 double dz, min = opt->min, max = opt->max, displAv, temp, distance, ztot, ztot_half, w, weight;
2933 dz = (max-min)/bins;
2934 ztot = opt->max-min;
2937 /* Compute average displacement from histograms */
2938 for (j = 0; j < nWindows; ++j)
2940 snew(window[j].forceAv, window[j].nPull);
2941 for (k = 0; k < window[j].nPull; ++k)
2945 for (i = 0; i < opt->bins; ++i)
2947 temp = (1.0*i+0.5)*dz+min;
2948 distance = temp - window[j].pos[k];
2950 { /* in cyclic wham: */
2951 if (distance > ztot_half) /* |distance| < ztot_half */
2955 else if (distance < -ztot_half)
2960 w = window[j].Histo[k][i]/window[j].g[k];
2961 displAv += w*distance;
2963 /* Are we near min or max? We are getting wrong forces from the histgrams since
2964 the histograms are zero outside [min,max). Therefore, assume that the position
2965 on the other side of the histomgram center is equally likely. */
2968 posmirrored = window[j].pos[k]-distance;
2969 if (posmirrored >= max || posmirrored < min)
2971 displAv += -w*distance;
2978 /* average force from average displacement */
2979 window[j].forceAv[k] = displAv*window[j].k[k];
2980 /* sigma from average square displacement */
2981 /* window[j].sigma [k] = sqrt(displAv2); */
2982 /* printf("Win %d, sigma = %f\n",j,sqrt(displAv2)); */
2988 * Check if the complete reaction coordinate is covered by the histograms
2990 static void checkReactionCoordinateCovered(t_UmbrellaWindow *window, int nwins,
2991 t_UmbrellaOptions *opt)
2993 int i, ig, j, bins = opt->bins, bBoundary;
2994 real avcount = 0, z, relcount, *count;
2995 snew(count, opt->bins);
2997 for (j = 0; j < opt->bins; ++j)
2999 for (i = 0; i < nwins; i++)
3001 for (ig = 0; ig < window[i].nPull; ig++)
3003 count[j] += window[i].Histo[ig][j];
3006 avcount += 1.0*count[j];
3009 for (j = 0; j < bins; ++j)
3011 relcount = count[j]/avcount;
3012 z = (j+0.5)*opt->dz+opt->min;
3013 bBoundary = ( j<bins/20 || (bins-j)>bins/20 );
3014 /* check for bins with no data */
3017 fprintf(stderr, "\nWARNING, no data point in bin %d (z=%g) !\n"
3018 "You may not get a reasonable profile. Check your histograms!\n", j, z);
3020 /* and check for poor sampling */
3021 else if (relcount < 0.005 && !bBoundary)
3023 fprintf(stderr, "Warning, poor sampling bin %d (z=%g). Check your histograms!\n", j, z);
3029 /*! \brief Compute initial potential by integrating the average force
3031 * This speeds up the convergence by roughly a factor of 2
3033 static void guessPotByIntegration(t_UmbrellaWindow *window, int nWindows, t_UmbrellaOptions *opt, const char *xlabel)
3035 int i, j, ig, bins = opt->bins, nHist, winmin, groupmin;
3036 double dz, min = opt->min, *pot, pos, hispos, dist, diff, fAv, distmin, *f;
3039 dz = (opt->max-min)/bins;
3041 printf("Getting initial potential by integration.\n");
3043 /* Compute average displacement from histograms */
3044 computeAverageForce(window, nWindows, opt);
3046 /* Get force for each bin from all histograms in this bin, or, alternatively,
3047 if no histograms are inside this bin, from the closest histogram */
3050 for (j = 0; j < opt->bins; ++j)
3052 pos = (1.0*j+0.5)*dz+min;
3056 groupmin = winmin = 0;
3057 for (i = 0; i < nWindows; i++)
3059 for (ig = 0; ig < window[i].nPull; ig++)
3061 hispos = window[i].pos[ig];
3062 dist = std::abs(hispos-pos);
3063 /* average force within bin */
3067 fAv += window[i].forceAv[ig];
3069 /* at the same time, remember closest histogram */
3078 /* if no histogram found in this bin, use closest histogram */
3085 fAv = window[winmin].forceAv[groupmin];
3089 for (j = 1; j < opt->bins; ++j)
3091 pot[j] = pot[j-1] - 0.5*dz*(f[j-1]+f[j]);
3094 /* cyclic wham: linearly correct possible offset */
3097 diff = (pot[bins-1]-pot[0])/(bins-1);
3098 for (j = 1; j < opt->bins; ++j)
3105 fp = xvgropen("pmfintegrated.xvg", "PMF from force integration", xlabel, "PMF (kJ/mol)", opt->oenv);
3106 for (j = 0; j < opt->bins; ++j)
3108 fprintf(fp, "%g %g\n", (j+0.5)*dz+opt->min, pot[j]);
3111 printf("verbose mode: wrote %s with PMF from interated forces\n", "pmfintegrated.xvg");
3114 /* get initial z=exp(-F[i]/kT) from integrated potential, where F[i] denote the free
3115 energy offsets which are usually determined by wham
3116 First: turn pot into probabilities:
3118 for (j = 0; j < opt->bins; ++j)
3120 pot[j] = std::exp(-pot[j]/(BOLTZ*opt->Temperature));
3122 calc_z(pot, window, nWindows, opt, TRUE);
3128 //! Count number of words in an line
3129 static int wordcount(char *ptr)
3134 if (std::strlen(ptr) == 0)
3138 /* fprintf(stderr,"ptr='%s'\n",ptr); */
3140 for (i = 0; (ptr[i] != '\0'); i++)
3142 is[cur] = isspace(ptr[i]);
3143 if ((i > 0) && (is[cur] && !is[1-cur]))
3152 /*! \brief Read input file for pull group selection (option -is)
3154 * TO DO: ptr=fgets(...) is never freed (small memory leak)
3156 static void readPullCoordSelection(t_UmbrellaOptions *opt, char **fnTpr, int nTpr)
3159 int i, iline, n, len = STRLEN, temp;
3160 char *ptr = nullptr, *tmpbuf = nullptr;
3161 char fmt[1024], fmtign[1024];
3162 int block = 1, sizenow;
3164 fp = gmx_ffopen(opt->fnCoordSel, "r");
3165 opt->coordsel = nullptr;
3170 while ( (ptr = fgets3(fp, tmpbuf, &len)) != nullptr)
3175 if (iline >= sizenow)
3178 srenew(opt->coordsel, sizenow);
3180 opt->coordsel[iline].n = n;
3181 opt->coordsel[iline].nUse = 0;
3182 snew(opt->coordsel[iline].bUse, n);
3185 for (i = 0; i < n; i++)
3187 std::strcpy(fmt, fmtign);
3188 std::strcat(fmt, "%d");
3189 if (sscanf(ptr, fmt, &temp))
3191 opt->coordsel[iline].bUse[i] = (temp > 0);
3192 if (opt->coordsel[iline].bUse[i])
3194 opt->coordsel[iline].nUse++;
3197 std::strcat(fmtign, "%*s");
3201 opt->nCoordsel = iline;
3202 if (nTpr != opt->nCoordsel)
3204 gmx_fatal(FARGS, "Found %d tpr files but %d lines in %s\n", nTpr, opt->nCoordsel,
3208 printf("\nUse only these pull coordinates:\n");
3209 for (iline = 0; iline < nTpr; iline++)
3211 printf("%s (%d of %d coordinates):", fnTpr[iline], opt->coordsel[iline].nUse, opt->coordsel[iline].n);
3212 for (i = 0; i < opt->coordsel[iline].n; i++)
3214 if (opt->coordsel[iline].bUse[i])
3227 #define WHAMBOOLXOR(a, b) ( ((!(a)) && (b)) || ((a) && (!(b))))
3229 //! Number of elements in fnm (used for command line parsing)
3230 #define NFILE asize(fnm)
3232 //! The main gmx wham routine
3233 int gmx_wham(int argc, char *argv[])
3235 const char *desc[] = {
3236 "[THISMODULE] is an analysis program that implements the Weighted",
3237 "Histogram Analysis Method (WHAM). It is intended to analyze",
3238 "output files generated by umbrella sampling simulations to ",
3239 "compute a potential of mean force (PMF).[PAR]",
3241 "[THISMODULE] is currently not fully up to date. It only supports pull setups",
3242 "where the first pull coordinate(s) is/are umbrella pull coordinates",
3243 "and, if multiple coordinates need to be analyzed, all used the same",
3244 "geometry and dimensions. In most cases this is not an issue.[PAR]",
3245 "At present, three input modes are supported.",
3247 "* With option [TT]-it[tt], the user provides a file which contains the",
3248 " file names of the umbrella simulation run-input files ([REF].tpr[ref] files),",
3249 " AND, with option [TT]-ix[tt], a file which contains file names of",
3250 " the pullx [TT]mdrun[tt] output files. The [REF].tpr[ref] and pullx files must",
3251 " be in corresponding order, i.e. the first [REF].tpr[ref] created the",
3252 " first pullx, etc.",
3253 "* Same as the previous input mode, except that the the user",
3254 " provides the pull force output file names ([TT]pullf.xvg[tt]) with option [TT]-if[tt].",
3255 " From the pull force the position in the umbrella potential is",
3256 " computed. This does not work with tabulated umbrella potentials.",
3257 "* With option [TT]-ip[tt], the user provides file names of (gzipped) [REF].pdo[ref] files, i.e.",
3258 " the GROMACS 3.3 umbrella output files. If you have some unusual",
3259 " reaction coordinate you may also generate your own [REF].pdo[ref] files and",
3260 " feed them with the [TT]-ip[tt] option into to [THISMODULE]. The [REF].pdo[ref] file header",
3261 " must be similar to the following::",
3264 " # Component selection: 0 0 1",
3266 " # Ref. Group 'TestAtom'",
3267 " # Nr. of pull groups 2",
3268 " # Group 1 'GR1' Umb. Pos. 5.0 Umb. Cons. 1000.0",
3269 " # Group 2 'GR2' Umb. Pos. 2.0 Umb. Cons. 500.0",
3272 " The number of pull groups, umbrella positions, force constants, and names ",
3273 " may (of course) differ. Following the header, a time column and ",
3274 " a data column for each pull group follows (i.e. the displacement",
3275 " with respect to the umbrella center). Up to four pull groups are possible ",
3276 " per [REF].pdo[ref] file at present.[PAR]",
3277 "By default, all pull coordinates found in all pullx/pullf files are used in WHAM. If only ",
3278 "some of the pull coordinates should be used, a pull coordinate selection file (option [TT]-is[tt]) can ",
3279 "be provided. The selection file must contain one line for each tpr file in tpr-files.dat.",
3280 "Each of these lines must contain one digit (0 or 1) for each pull coordinate in the tpr file. ",
3281 "Here, 1 indicates that the pull coordinate is used in WHAM, and 0 means it is omitted. Example:",
3282 "If you have three tpr files, each containing 4 pull coordinates, but only pull coordinates 1 and 2 should be ",
3283 "used, coordsel.dat looks like this::",
3289 "By default, the output files are::",
3291 " [TT]-o[tt] PMF output file",
3292 " [TT]-hist[tt] Histograms output file",
3294 "Always check whether the histograms sufficiently overlap.[PAR]",
3295 "The umbrella potential is assumed to be harmonic and the force constants are ",
3296 "read from the [REF].tpr[ref] or [REF].pdo[ref] files. If a non-harmonic umbrella force was applied ",
3297 "a tabulated potential can be provided with [TT]-tab[tt].",
3302 "* [TT]-bins[tt] Number of bins used in analysis",
3303 "* [TT]-temp[tt] Temperature in the simulations",
3304 "* [TT]-tol[tt] Stop iteration if profile (probability) changed less than tolerance",
3305 "* [TT]-auto[tt] Automatic determination of boundaries",
3306 "* [TT]-min,-max[tt] Boundaries of the profile",
3308 "The data points that are used to compute the profile",
3309 "can be restricted with options [TT]-b[tt], [TT]-e[tt], and [TT]-dt[tt]. ",
3310 "Adjust [TT]-b[tt] to ensure sufficient equilibration in each ",
3311 "umbrella window.[PAR]",
3312 "With [TT]-log[tt] (default) the profile is written in energy units, otherwise ",
3313 "(with [TT]-nolog[tt]) as probability. The unit can be specified with [TT]-unit[tt]. ",
3314 "With energy output, the energy in the first bin is defined to be zero. ",
3315 "If you want the free energy at a different ",
3316 "position to be zero, set [TT]-zprof0[tt] (useful with bootstrapping, see below).[PAR]",
3317 "For cyclic or periodic reaction coordinates (dihedral angle, channel PMF",
3318 "without osmotic gradient), the option [TT]-cycl[tt] is useful.",
3319 "[THISMODULE] will make use of the",
3320 "periodicity of the system and generate a periodic PMF. The first and the last bin of the",
3321 "reaction coordinate will assumed be be neighbors.[PAR]",
3322 "Option [TT]-sym[tt] symmetrizes the profile around z=0 before output, ",
3323 "which may be useful for, e.g. membranes.",
3328 "If available, the number of OpenMP threads used by gmx wham can be controlled by setting",
3329 "the [TT]OMP_NUM_THREADS[tt] environment variable.",
3334 "With [TT]-ac[tt], [THISMODULE] estimates the integrated autocorrelation ",
3335 "time (IACT) [GRK]tau[grk] for each umbrella window and weights the respective ",
3336 "window with 1/[1+2*[GRK]tau[grk]/dt]. The IACTs are written ",
3337 "to the file defined with [TT]-oiact[tt]. In verbose mode, all ",
3338 "autocorrelation functions (ACFs) are written to [TT]hist_autocorr.xvg[tt]. ",
3339 "Because the IACTs can be severely underestimated in case of limited ",
3340 "sampling, option [TT]-acsig[tt] allows one to smooth the IACTs along the ",
3341 "reaction coordinate with a Gaussian ([GRK]sigma[grk] provided with [TT]-acsig[tt], ",
3342 "see output in [TT]iact.xvg[tt]). Note that the IACTs are estimated by simple ",
3343 "integration of the ACFs while the ACFs are larger 0.05.",
3344 "If you prefer to compute the IACTs by a more sophisticated (but possibly ",
3345 "less robust) method such as fitting to a double exponential, you can ",
3346 "compute the IACTs with [gmx-analyze] and provide them to [THISMODULE] with the file ",
3347 "[TT]iact-in.dat[tt] (option [TT]-iiact[tt]), which should contain one line per ",
3348 "input file ([REF].pdo[ref] or pullx/f file) and one column per pull coordinate in the respective file.",
3353 "Statistical errors may be estimated with bootstrap analysis. Use it with care, ",
3354 "otherwise the statistical error may be substantially underestimated. ",
3355 "More background and examples for the bootstrap technique can be found in ",
3356 "Hub, de Groot and Van der Spoel, JCTC (2010) 6: 3713-3720.",
3357 "[TT]-nBootstrap[tt] defines the number of bootstraps (use, e.g., 100). ",
3358 "Four bootstrapping methods are supported and ",
3359 "selected with [TT]-bs-method[tt].",
3361 "* [TT]b-hist[tt] Default: complete histograms are considered as independent ",
3362 " data points, and the bootstrap is carried out by assigning random weights to the ",
3363 " histograms (\"Bayesian bootstrap\"). Note that each point along the reaction coordinate",
3364 " must be covered by multiple independent histograms (e.g. 10 histograms), otherwise the ",
3365 " statistical error is underestimated.",
3366 "* [TT]hist[tt] Complete histograms are considered as independent data points. ",
3367 " For each bootstrap, N histograms are randomly chosen from the N given histograms ",
3368 " (allowing duplication, i.e. sampling with replacement).",
3369 " To avoid gaps without data along the reaction coordinate blocks of histograms ",
3370 " ([TT]-histbs-block[tt]) may be defined. In that case, the given histograms are ",
3371 " divided into blocks and only histograms within each block are mixed. Note that ",
3372 " the histograms within each block must be representative for all possible histograms, ",
3373 " otherwise the statistical error is underestimated.",
3374 "* [TT]traj[tt] The given histograms are used to generate new random trajectories,",
3375 " such that the generated data points are distributed according the given histograms ",
3376 " and properly autocorrelated. The autocorrelation time (ACT) for each window must be ",
3377 " known, so use [TT]-ac[tt] or provide the ACT with [TT]-iiact[tt]. If the ACT of all ",
3378 " windows are identical (and known), you can also provide them with [TT]-bs-tau[tt]. ",
3379 " Note that this method may severely underestimate the error in case of limited sampling, ",
3380 " that is if individual histograms do not represent the complete phase space at ",
3381 " the respective positions.",
3382 "* [TT]traj-gauss[tt] The same as method [TT]traj[tt], but the trajectories are ",
3383 " not bootstrapped from the umbrella histograms but from Gaussians with the average ",
3384 " and width of the umbrella histograms. That method yields similar error estimates ",
3385 " like method [TT]traj[tt].",
3387 "Bootstrapping output:",
3389 "* [TT]-bsres[tt] Average profile and standard deviations",
3390 "* [TT]-bsprof[tt] All bootstrapping profiles",
3392 "With [TT]-vbs[tt] (verbose bootstrapping), the histograms of each bootstrap are written, ",
3393 "and, with bootstrap method [TT]traj[tt], the cumulative distribution functions of ",
3397 const char *en_unit[] = {nullptr, "kJ", "kCal", "kT", nullptr};
3398 const char *en_unit_label[] = {"", "E (kJ mol\\S-1\\N)", "E (kcal mol\\S-1\\N)", "E (kT)", nullptr};
3399 const char *en_bsMethod[] = { nullptr, "b-hist", "hist", "traj", "traj-gauss", nullptr };
3400 static t_UmbrellaOptions opt;
3403 { "-min", FALSE, etREAL, {&opt.min},
3404 "Minimum coordinate in profile"},
3405 { "-max", FALSE, etREAL, {&opt.max},
3406 "Maximum coordinate in profile"},
3407 { "-auto", FALSE, etBOOL, {&opt.bAuto},
3408 "Determine min and max automatically"},
3409 { "-bins", FALSE, etINT, {&opt.bins},
3410 "Number of bins in profile"},
3411 { "-temp", FALSE, etREAL, {&opt.Temperature},
3413 { "-tol", FALSE, etREAL, {&opt.Tolerance},
3415 { "-v", FALSE, etBOOL, {&opt.verbose},
3417 { "-b", FALSE, etREAL, {&opt.tmin},
3418 "First time to analyse (ps)"},
3419 { "-e", FALSE, etREAL, {&opt.tmax},
3420 "Last time to analyse (ps)"},
3421 { "-dt", FALSE, etREAL, {&opt.dt},
3422 "Analyse only every dt ps"},
3423 { "-histonly", FALSE, etBOOL, {&opt.bHistOnly},
3424 "Write histograms and exit"},
3425 { "-boundsonly", FALSE, etBOOL, {&opt.bBoundsOnly},
3426 "Determine min and max and exit (with [TT]-auto[tt])"},
3427 { "-log", FALSE, etBOOL, {&opt.bLog},
3428 "Calculate the log of the profile before printing"},
3429 { "-unit", FALSE, etENUM, {en_unit},
3430 "Energy unit in case of log output" },
3431 { "-zprof0", FALSE, etREAL, {&opt.zProf0},
3432 "Define profile to 0.0 at this position (with [TT]-log[tt])"},
3433 { "-cycl", FALSE, etBOOL, {&opt.bCycl},
3434 "Create cyclic/periodic profile. Assumes min and max are the same point."},
3435 { "-sym", FALSE, etBOOL, {&opt.bSym},
3436 "Symmetrize profile around z=0"},
3437 { "-hist-eq", FALSE, etBOOL, {&opt.bHistEq},
3438 "HIDDENEnforce equal weight for all histograms. (Non-Weighed-HAM)"},
3439 { "-ac", FALSE, etBOOL, {&opt.bCalcTauInt},
3440 "Calculate integrated autocorrelation times and use in wham"},
3441 { "-acsig", FALSE, etREAL, {&opt.sigSmoothIact},
3442 "Smooth autocorrelation times along reaction coordinate with Gaussian of this [GRK]sigma[grk]"},
3443 { "-ac-trestart", FALSE, etREAL, {&opt.acTrestart},
3444 "When computing autocorrelation functions, restart computing every .. (ps)"},
3445 { "-acred", FALSE, etBOOL, {&opt.bAllowReduceIact},
3446 "HIDDENWhen smoothing the ACTs, allows one to reduce ACTs. Otherwise, only increase ACTs "
3447 "during smoothing"},
3448 { "-nBootstrap", FALSE, etINT, {&opt.nBootStrap},
3449 "nr of bootstraps to estimate statistical uncertainty (e.g., 200)" },
3450 { "-bs-method", FALSE, etENUM, {en_bsMethod},
3451 "Bootstrap method" },
3452 { "-bs-tau", FALSE, etREAL, {&opt.tauBootStrap},
3453 "Autocorrelation time (ACT) assumed for all histograms. Use option [TT]-ac[tt] if ACT is unknown."},
3454 { "-bs-seed", FALSE, etINT, {&opt.bsSeed},
3455 "Seed for bootstrapping. (-1 = use time)"},
3456 { "-histbs-block", FALSE, etINT, {&opt.histBootStrapBlockLength},
3457 "When mixing histograms only mix within blocks of [TT]-histbs-block[tt]."},
3458 { "-vbs", FALSE, etBOOL, {&opt.bs_verbose},
3459 "Verbose bootstrapping. Print the CDFs and a histogram file for each bootstrap."},
3460 { "-stepout", FALSE, etINT, {&opt.stepchange},
3461 "HIDDENWrite maximum change every ... (set to 1 with [TT]-v[tt])"},
3462 { "-updateContr", FALSE, etINT, {&opt.stepUpdateContrib},
3463 "HIDDENUpdate table with significan contributions to WHAM every ... iterations"},
3467 { efDAT, "-ix", "pullx-files", ffOPTRD}, /* wham input: pullf.xvg's and tprs */
3468 { efDAT, "-if", "pullf-files", ffOPTRD}, /* wham input: pullf.xvg's and tprs */
3469 { efDAT, "-it", "tpr-files", ffOPTRD}, /* wham input: tprs */
3470 { efDAT, "-ip", "pdo-files", ffOPTRD}, /* wham input: pdo files (gmx3 style) */
3471 { efDAT, "-is", "coordsel", ffOPTRD}, /* input: select pull coords to use */
3472 { efXVG, "-o", "profile", ffWRITE }, /* output file for profile */
3473 { efXVG, "-hist", "histo", ffWRITE}, /* output file for histograms */
3474 { efXVG, "-oiact", "iact", ffOPTWR}, /* writing integrated autocorrelation times */
3475 { efDAT, "-iiact", "iact-in", ffOPTRD}, /* reading integrated autocorrelation times */
3476 { efXVG, "-bsres", "bsResult", ffOPTWR}, /* average and errors of bootstrap analysis */
3477 { efXVG, "-bsprof", "bsProfs", ffOPTWR}, /* output file for bootstrap profiles */
3478 { efDAT, "-tab", "umb-pot", ffOPTRD}, /* Tabulated umbrella potential (if not harmonic) */
3481 int i, j, l, nfiles, nwins, nfiles2;
3482 t_UmbrellaHeader header;
3483 t_UmbrellaWindow * window = nullptr;
3484 double *profile, maxchange = 1e20;
3485 gmx_bool bMinSet, bMaxSet, bAutoSet, bExact = FALSE;
3486 char **fninTpr, **fninPull, **fninPdo;
3488 FILE *histout, *profout;
3489 char xlabel[STRLEN], ylabel[256], title[256];
3492 opt.verbose = FALSE;
3493 opt.bHistOnly = FALSE;
3502 opt.coordsel = nullptr;
3504 /* bootstrapping stuff */
3506 opt.bsMethod = bsMethod_hist;
3507 opt.tauBootStrap = 0.0;
3509 opt.histBootStrapBlockLength = 8;
3510 opt.bs_verbose = FALSE;
3515 opt.Temperature = 298;
3516 opt.Tolerance = 1e-6;
3517 opt.bBoundsOnly = FALSE;
3519 opt.bCalcTauInt = FALSE;
3520 opt.sigSmoothIact = 0.0;
3521 opt.bAllowReduceIact = TRUE;
3522 opt.bInitPotByIntegration = TRUE;
3523 opt.acTrestart = 1.0;
3524 opt.stepchange = 100;
3525 opt.stepUpdateContrib = 100;
3527 if (!parse_common_args(&argc, argv, 0,
3528 NFILE, fnm, asize(pa), pa, asize(desc), desc, 0, nullptr, &opt.oenv))
3533 opt.unit = nenum(en_unit);
3534 opt.bsMethod = nenum(en_bsMethod);
3536 opt.bProf0Set = opt2parg_bSet("-zprof0", asize(pa), pa);
3538 opt.bTab = opt2bSet("-tab", NFILE, fnm);
3539 opt.bPdo = opt2bSet("-ip", NFILE, fnm);
3540 opt.bTpr = opt2bSet("-it", NFILE, fnm);
3541 opt.bPullx = opt2bSet("-ix", NFILE, fnm);
3542 opt.bPullf = opt2bSet("-if", NFILE, fnm);
3543 opt.bTauIntGiven = opt2bSet("-iiact", NFILE, fnm);
3544 if (opt.bTab && opt.bPullf)
3546 gmx_fatal(FARGS, "Force input does not work with tabulated potentials. "
3547 "Provide pullx.xvg or pdo files!");
3550 if (!opt.bPdo && !WHAMBOOLXOR(opt.bPullx, opt.bPullf))
3552 gmx_fatal(FARGS, "Give either pullx (-ix) OR pullf (-if) data. Not both.");
3554 if (!opt.bPdo && !(opt.bTpr || opt.bPullf || opt.bPullx))
3556 gmx_fatal(FARGS, "gmx wham supports three input modes, pullx, pullf, or pdo file input."
3557 "\n\n Check gmx wham -h !");
3560 opt.fnPdo = opt2fn("-ip", NFILE, fnm);
3561 opt.fnTpr = opt2fn("-it", NFILE, fnm);
3562 opt.fnPullf = opt2fn("-if", NFILE, fnm);
3563 opt.fnPullx = opt2fn("-ix", NFILE, fnm);
3564 opt.fnCoordSel = opt2fn_null("-is", NFILE, fnm);
3566 bMinSet = opt2parg_bSet("-min", asize(pa), pa);
3567 bMaxSet = opt2parg_bSet("-max", asize(pa), pa);
3568 bAutoSet = opt2parg_bSet("-auto", asize(pa), pa);
3569 if ( (bMinSet || bMaxSet) && bAutoSet)
3571 gmx_fatal(FARGS, "With -auto, do not give -min or -max\n");
3574 if ( (bMinSet && !bMaxSet) || (!bMinSet && bMaxSet))
3576 gmx_fatal(FARGS, "When giving -min, you must give -max (and vice versa), too\n");
3579 if (bMinSet && opt.bAuto)
3581 printf("Note: min and max given, switching off -auto.\n");
3585 if (opt.bTauIntGiven && opt.bCalcTauInt)
3587 gmx_fatal(FARGS, "Either read (option -iiact) or calculate (option -ac) the\n"
3588 "the autocorrelation times. Not both.");
3591 if (opt.tauBootStrap > 0.0 && opt2parg_bSet("-ac", asize(pa), pa))
3593 gmx_fatal(FARGS, "Either compute autocorrelation times (ACTs) (option -ac) or "
3594 "provide it with -bs-tau for bootstrapping. Not Both.\n");
3596 if (opt.tauBootStrap > 0.0 && opt2bSet("-iiact", NFILE, fnm))
3598 gmx_fatal(FARGS, "Either provide autocorrelation times (ACTs) with file iact-in.dat "
3599 "(option -iiact) or define all ACTs with -bs-tau for bootstrapping\n. Not Both.");
3602 /* Reading gmx4/gmx5 pull output and tpr files */
3603 if (opt.bTpr || opt.bPullf || opt.bPullx)
3605 read_wham_in(opt.fnTpr, &fninTpr, &nfiles, &opt);
3607 fnPull = opt.bPullf ? opt.fnPullf : opt.fnPullx;
3608 read_wham_in(fnPull, &fninPull, &nfiles2, &opt);
3609 printf("Found %d tpr and %d pull %s files in %s and %s, respectively\n",
3610 nfiles, nfiles2, opt.bPullf ? "force" : "position", opt.fnTpr, fnPull);
3611 if (nfiles != nfiles2)
3613 gmx_fatal(FARGS, "Found %d file names in %s, but %d in %s\n", nfiles,
3614 opt.fnTpr, nfiles2, fnPull);
3617 /* Read file that selects the pull group to be used */
3618 if (opt.fnCoordSel != nullptr)
3620 readPullCoordSelection(&opt, fninTpr, nfiles);
3623 window = initUmbrellaWindows(nfiles);
3624 read_tpr_pullxf_files(fninTpr, fninPull, nfiles, &header, window, &opt);
3627 { /* reading pdo files */
3628 if (opt.fnCoordSel != nullptr)
3630 gmx_fatal(FARGS, "Reading a -is file is not supported with PDO input files.\n"
3631 "Use awk or a similar tool to pick the required pull groups from your PDO files\n");
3633 read_wham_in(opt.fnPdo, &fninPdo, &nfiles, &opt);
3634 printf("Found %d pdo files in %s\n", nfiles, opt.fnPdo);
3635 window = initUmbrellaWindows(nfiles);
3636 read_pdo_files(fninPdo, nfiles, &header, window, &opt);
3639 /* It is currently assumed that all pull coordinates have the same geometry, so they also have the same coordinate units.
3640 We can therefore get the units for the xlabel from the first coordinate. */
3641 sprintf(xlabel, "\\xx\\f{} (%s)", header.pcrd[0].coord_unit);
3645 /* enforce equal weight for all histograms? */
3648 enforceEqualWeights(window, nwins);
3651 /* write histograms */
3652 histout = xvgropen(opt2fn("-hist", NFILE, fnm), "Umbrella histograms",
3653 xlabel, "count", opt.oenv);
3654 for (l = 0; l < opt.bins; ++l)
3656 fprintf(histout, "%e\t", (l+0.5)/opt.bins*(opt.max-opt.min)+opt.min);
3657 for (i = 0; i < nwins; ++i)
3659 for (j = 0; j < window[i].nPull; ++j)
3661 fprintf(histout, "%e\t", window[i].Histo[j][l]);
3664 fprintf(histout, "\n");
3667 printf("Wrote %s\n", opt2fn("-hist", NFILE, fnm));
3670 printf("Wrote histograms to %s, now exiting.\n", opt2fn("-hist", NFILE, fnm));
3674 /* Using tabulated umbrella potential */
3677 setup_tab(opt2fn("-tab", NFILE, fnm), &opt);
3680 /* Integrated autocorrelation times provided ? */
3681 if (opt.bTauIntGiven)
3683 readIntegratedAutocorrelationTimes(window, nwins, opt2fn("-iiact", NFILE, fnm));
3686 /* Compute integrated autocorrelation times */
3687 if (opt.bCalcTauInt)
3689 calcIntegratedAutocorrelationTimes(window, nwins, &opt, opt2fn("-oiact", NFILE, fnm), xlabel);
3692 /* calc average and sigma for each histogram
3693 (maybe required for bootstrapping. If not, this is fast anyhow) */
3694 if (opt.nBootStrap && opt.bsMethod == bsMethod_trajGauss)
3696 averageSigma(window, nwins);
3699 /* Get initial potential by simple integration */
3700 if (opt.bInitPotByIntegration)
3702 guessPotByIntegration(window, nwins, &opt, xlabel);
3705 /* Check if complete reaction coordinate is covered */
3706 checkReactionCoordinateCovered(window, nwins, &opt);
3708 /* Calculate profile */
3709 snew(profile, opt.bins);
3717 if ( (i%opt.stepUpdateContrib) == 0)
3719 setup_acc_wham(profile, window, nwins, &opt);
3721 if (maxchange < opt.Tolerance)
3724 /* if (opt.verbose) */
3725 printf("Switched to exact iteration in iteration %d\n", i);
3727 calc_profile(profile, window, nwins, &opt, bExact);
3728 if (((i%opt.stepchange) == 0 || i == 1) && i != 0)
3730 printf("\t%4d) Maximum change %e\n", i, maxchange);
3734 while ( (maxchange = calc_z(profile, window, nwins, &opt, bExact)) > opt.Tolerance || !bExact);
3735 printf("Converged in %d iterations. Final maximum change %g\n", i, maxchange);
3737 /* calc error from Kumar's formula */
3738 /* Unclear how the error propagates along reaction coordinate, therefore
3740 /* calc_error_kumar(profile,window, nwins,&opt); */
3742 /* Write profile in energy units? */
3745 prof_normalization_and_unit(profile, &opt);
3746 std::strcpy(ylabel, en_unit_label[opt.unit]);
3747 std::strcpy(title, "Umbrella potential");
3751 std::strcpy(ylabel, "Density of states");
3752 std::strcpy(title, "Density of states");
3755 /* symmetrize profile around z=0? */
3758 symmetrizeProfile(profile, &opt);
3761 /* write profile or density of states */
3762 profout = xvgropen(opt2fn("-o", NFILE, fnm), title, xlabel, ylabel, opt.oenv);
3763 for (i = 0; i < opt.bins; ++i)
3765 fprintf(profout, "%e\t%e\n", (i+0.5)/opt.bins*(opt.max-opt.min)+opt.min, profile[i]);
3768 printf("Wrote %s\n", opt2fn("-o", NFILE, fnm));
3770 /* Bootstrap Method */
3773 do_bootstrapping(opt2fn("-bsres", NFILE, fnm), opt2fn("-bsprof", NFILE, fnm),
3774 opt2fn("-hist", NFILE, fnm),
3775 xlabel, ylabel, profile, window, nwins, &opt);
3779 freeUmbrellaWindows(window, nfiles);
3781 printf("\nIn case you use results from gmx wham for a publication, please cite:\n");
3782 please_cite(stdout, "Hub2010");