md.cpp

/*
 * This file is part of the GROMACS molecular simulation package.
 *
 * Copyright (c) 1991-2000, University of Groningen, The Netherlands.
 * Copyright (c) 2001-2004, The GROMACS development team.
 * Copyright (c) 2011,2012,2013,2014,2015,2016,2017,2018, by the GROMACS development team, led by
 * Mark Abraham, David van der Spoel, Berk Hess, and Erik Lindahl,
 * and including many others, as listed in the AUTHORS file in the
 * top-level source directory and at http://www.gromacs.org.
 *
 * GROMACS is free software; you can redistribute it and/or
 * modify it under the terms of the GNU Lesser General Public License
 * as published by the Free Software Foundation; either version 2.1
 * of the License, or (at your option) any later version.
 *
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 * MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE.  See the GNU
 * Lesser General Public License for more details.
 *
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 */
#include "gmxpre.h"

#include "md.h"

#include "config.h"

#include <stdio.h>
#include <stdlib.h>

#include <cmath>

#include <algorithm>
#include <memory>

#include "thread_mpi/threads.h"

#include "gromacs/awh/awh.h"
#include "gromacs/commandline/filenm.h"
#include "gromacs/compat/make_unique.h"
#include "gromacs/domdec/domdec.h"
#include "gromacs/domdec/domdec_network.h"
#include "gromacs/domdec/domdec_struct.h"
#include "gromacs/essentialdynamics/edsam.h"
#include "gromacs/ewald/pme.h"
#include "gromacs/ewald/pme-load-balancing.h"
#include "gromacs/fileio/trxio.h"
#include "gromacs/gmxlib/network.h"
#include "gromacs/gmxlib/nrnb.h"
#include "gromacs/gpu_utils/gpu_utils.h"
#include "gromacs/imd/imd.h"
#include "gromacs/listed-forces/manage-threading.h"
#include "gromacs/math/functions.h"
#include "gromacs/math/units.h"
#include "gromacs/math/utilities.h"
#include "gromacs/math/vec.h"
#include "gromacs/math/vectypes.h"
#include "gromacs/mdlib/compute_io.h"
#include "gromacs/mdlib/constr.h"
#include "gromacs/mdlib/ebin.h"
#include "gromacs/mdlib/expanded.h"
#include "gromacs/mdlib/force.h"
#include "gromacs/mdlib/force_flags.h"
#include "gromacs/mdlib/forcerec.h"
#include "gromacs/mdlib/md_support.h"
#include "gromacs/mdlib/mdatoms.h"
#include "gromacs/mdlib/mdebin.h"
#include "gromacs/mdlib/mdoutf.h"
#include "gromacs/mdlib/mdrun.h"
#include "gromacs/mdlib/mdsetup.h"
#include "gromacs/mdlib/nb_verlet.h"
#include "gromacs/mdlib/nbnxn_gpu_data_mgmt.h"
#include "gromacs/mdlib/ns.h"
#include "gromacs/mdlib/shellfc.h"
#include "gromacs/mdlib/sighandler.h"
#include "gromacs/mdlib/sim_util.h"
#include "gromacs/mdlib/simulationsignal.h"
#include "gromacs/mdlib/tgroup.h"
#include "gromacs/mdlib/trajectory_writing.h"
#include "gromacs/mdlib/update.h"
#include "gromacs/mdlib/vcm.h"
#include "gromacs/mdlib/vsite.h"
#include "gromacs/mdtypes/awh-history.h"
#include "gromacs/mdtypes/awh-params.h"
#include "gromacs/mdtypes/commrec.h"
#include "gromacs/mdtypes/df_history.h"
#include "gromacs/mdtypes/energyhistory.h"
#include "gromacs/mdtypes/fcdata.h"
#include "gromacs/mdtypes/forcerec.h"
#include "gromacs/mdtypes/group.h"
#include "gromacs/mdtypes/inputrec.h"
#include "gromacs/mdtypes/interaction_const.h"
#include "gromacs/mdtypes/md_enums.h"
#include "gromacs/mdtypes/mdatom.h"
#include "gromacs/mdtypes/observableshistory.h"
#include "gromacs/mdtypes/state.h"
#include "gromacs/pbcutil/mshift.h"
#include "gromacs/pbcutil/pbc.h"
#include "gromacs/pulling/pull.h"
#include "gromacs/swap/swapcoords.h"
#include "gromacs/timing/wallcycle.h"
#include "gromacs/timing/walltime_accounting.h"
#include "gromacs/topology/atoms.h"
#include "gromacs/topology/idef.h"
#include "gromacs/topology/mtop_util.h"
#include "gromacs/topology/topology.h"
#include "gromacs/trajectory/trajectoryframe.h"
#include "gromacs/utility/basedefinitions.h"
#include "gromacs/utility/cstringutil.h"
#include "gromacs/utility/fatalerror.h"
#include "gromacs/utility/logger.h"
#include "gromacs/utility/real.h"
#include "gromacs/utility/smalloc.h"
#include "gromacs/utility/stringutil.h"

#include "deform.h"
#include "membed.h"
#include "repl_ex.h"

/* PLUMED */
#include "../../../Plumed.h"
extern int    plumedswitch;
extern plumed plumedmain;
/* END PLUMED */

/* PLUMED HREX */
extern int plumed_hrex;
/* END PLUMED HREX */

#ifdef GMX_FAHCORE
#include "corewrap.h"
#endif

using gmx::SimulationSignaller;

/*! \brief Check whether bonded interactions are missing, if appropriate
 *
 * \param[in]    fplog                                  Log file pointer
 * \param[in]    cr                                     Communication object
 * \param[in]    totalNumberOfBondedInteractions        Result of the global reduction over the number of bonds treated in each domain
 * \param[in]    top_global                             Global topology for the error message
 * \param[in]    top_local                              Local topology for the error message
 * \param[in]    state                                  Global state for the error message
 * \param[inout] shouldCheckNumberOfBondedInteractions  Whether we should do the check.
 *
 * \return Nothing, except that shouldCheckNumberOfBondedInteractions
 * is always set to false after exit.
 */
static void checkNumberOfBondedInteractions(FILE *fplog, t_commrec *cr, int totalNumberOfBondedInteractions,
                                            gmx_mtop_t *top_global, gmx_localtop_t *top_local, t_state *state,
                                            bool *shouldCheckNumberOfBondedInteractions)
{
    if (*shouldCheckNumberOfBondedInteractions)
    {
        if (totalNumberOfBondedInteractions != cr->dd->nbonded_global)
        {
            dd_print_missing_interactions(fplog, cr, totalNumberOfBondedInteractions, top_global, top_local, state); // Does not return
        }
        *shouldCheckNumberOfBondedInteractions = false;
    }
}

static void reset_all_counters(FILE *fplog, const gmx::MDLogger &mdlog, t_commrec *cr,
                               gmx_int64_t step,
                               gmx_int64_t *step_rel, t_inputrec *ir,
                               gmx_wallcycle_t wcycle, t_nrnb *nrnb,
                               gmx_walltime_accounting_t walltime_accounting,
                               struct nonbonded_verlet_t *nbv,
                               struct gmx_pme_t *pme)
{
    char sbuf[STEPSTRSIZE];

    /* Reset all the counters related to performance over the run */
    GMX_LOG(mdlog.warning).asParagraph().appendTextFormatted(
            "step %s: resetting all time and cycle counters",
            gmx_step_str(step, sbuf));

    if (use_GPU(nbv))
    {
        nbnxn_gpu_reset_timings(nbv);
    }

    if (pme_gpu_task_enabled(pme))
    {
        pme_gpu_reset_timings(pme);
    }

    if (use_GPU(nbv) || pme_gpu_task_enabled(pme))
    {
        resetGpuProfiler();
    }

    wallcycle_stop(wcycle, ewcRUN);
    wallcycle_reset_all(wcycle);
    if (DOMAINDECOMP(cr))
    {
        reset_dd_statistics_counters(cr->dd);
    }
    init_nrnb(nrnb);
    ir->init_step += *step_rel;
    ir->nsteps    -= *step_rel;
    *step_rel      = 0;
    wallcycle_start(wcycle, ewcRUN);
    walltime_accounting_start(walltime_accounting);
    print_date_and_time(fplog, cr->nodeid, "Restarted time", gmx_gettime());
}

/*! \brief Copy the state from \p rerunFrame to \p globalState and, if requested, construct vsites
 *
 * \param[in]     rerunFrame      The trajectory frame to compute energy/forces for
 * \param[in,out] globalState     The global state container
 * \param[in]     constructVsites When true, vsite coordinates are constructed
 * \param[in]     vsite           Vsite setup, can be nullptr when \p constructVsites = false
 * \param[in]     idef            Topology parameters, used for constructing vsites
 * \param[in]     timeStep        Time step, used for constructing vsites
 * \param[in]     forceRec        Force record, used for constructing vsites
 * \param[in,out] graph           The molecular graph, used for constructing vsites when != nullptr
 * \param[in,out] warnWhenNoV     When true, issue a warning when no velocities are present in \p rerunFrame; is set to false when a warning was issued
 */
static void prepareRerunState(const t_trxframe  &rerunFrame,
                              t_state           *globalState,
                              bool               constructVsites,
                              const gmx_vsite_t *vsite,
                              const t_idef      &idef,
                              double             timeStep,
                              const t_forcerec  &forceRec,
                              t_graph           *graph,
                              gmx_bool          *warnWhenNoV)
{
    for (int i = 0; i < globalState->natoms; i++)
    {
        copy_rvec(rerunFrame.x[i], globalState->x[i]);
    }
    if (rerunFrame.bV)
    {
        for (int i = 0; i < globalState->natoms; i++)
        {
            copy_rvec(rerunFrame.v[i], globalState->v[i]);
        }
    }
    else
    {
        for (int i = 0; i < globalState->natoms; i++)
        {
            clear_rvec(globalState->v[i]);
        }
        if (*warnWhenNoV)
        {
            fprintf(stderr, "\nWARNING: Some frames do not contain velocities.\n"
                    "         Ekin, temperature and pressure are incorrect,\n"
                    "         the virial will be incorrect when constraints are present.\n"
                    "\n");
            *warnWhenNoV = FALSE;
        }
    }
    copy_mat(rerunFrame.box, globalState->box);

    if (constructVsites)
    {
        GMX_ASSERT(vsite, "Need valid vsite for constructing vsites");

        if (graph)
        {
            /* Following is necessary because the graph may get out of sync
             * with the coordinates if we only have every N'th coordinate set
             */
            mk_mshift(nullptr, graph, forceRec.ePBC, globalState->box, as_rvec_array(globalState->x.data()));
            shift_self(graph, globalState->box, as_rvec_array(globalState->x.data()));
        }
        construct_vsites(vsite, as_rvec_array(globalState->x.data()), timeStep, as_rvec_array(globalState->v.data()),
                         idef.iparams, idef.il,
                         forceRec.ePBC, forceRec.bMolPBC, nullptr, globalState->box);
        if (graph)
        {
            unshift_self(graph, globalState->box, as_rvec_array(globalState->x.data()));
        }
    }
}

/*! \libinternal
    \copydoc integrator_t (FILE *fplog, t_commrec *cr, const gmx::MDLogger &mdlog,
                           int nfile, const t_filenm fnm[],
                           const gmx_output_env_t *oenv,
                           const MdrunOptions &mdrunOptions,
                           gmx_vsite_t *vsite, gmx_constr_t constr,
                           gmx::IMDOutputProvider *outputProvider,
                           t_inputrec *inputrec,
                           gmx_mtop_t *top_global, t_fcdata *fcd,
                           t_state *state_global,
                           t_mdatoms *mdatoms,
                           t_nrnb *nrnb, gmx_wallcycle_t wcycle,
                           t_forcerec *fr,
                           const ReplicaExchangeParameters &replExParams,
                           gmx_membed_t *membed,
                           gmx_walltime_accounting_t walltime_accounting)
 */
double gmx::do_md(FILE *fplog, t_commrec *cr, const gmx::MDLogger &mdlog,
                  int nfile, const t_filenm fnm[],
                  const gmx_output_env_t *oenv,
                  const MdrunOptions &mdrunOptions,
                  gmx_vsite_t *vsite, gmx_constr_t constr,
                  gmx::IMDOutputProvider *outputProvider,
                  t_inputrec *ir,
                  gmx_mtop_t *top_global,
                  t_fcdata *fcd,
                  t_state *state_global,
                  ObservablesHistory *observablesHistory,
                  gmx::MDAtoms *mdAtoms,
                  t_nrnb *nrnb, gmx_wallcycle_t wcycle,
                  t_forcerec *fr,
                  const ReplicaExchangeParameters &replExParams,
                  gmx_membed_t *membed,
                  gmx_walltime_accounting_t walltime_accounting)
{
    /* Workaround for 2 bugs in release-2018.
     * NOTE: Proper fix is in release-2019, do not merge this change there.
     */
    if (ir->bExpanded && (EI_VV(ir->eI) ||
                          ir->expandedvals->nstexpanded % ir->nstcalcenergy != 0))
    {
        ir->nstcalcenergy = 1;
        std::string note =
            gmx::formatString("NOTE: There are issues with expanded ensemble and certain combination of nstexpanded and nstcalcenergy, setting nstcalcenergy to %d",
                              ir->nstcalcenergy);
        GMX_LOG(mdlog.warning).asParagraph().appendText(note);
    }

    gmx_mdoutf_t    outf = nullptr;
    gmx_int64_t     step, step_rel;
    double          elapsed_time;
    double          t, t0, lam0[efptNR];
    gmx_bool        bGStatEveryStep, bGStat, bCalcVir, bCalcEnerStep, bCalcEner;
    gmx_bool        bNS, bNStList, bSimAnn, bStopCM,
                    bFirstStep, bInitStep, bLastStep = FALSE,
                    bBornRadii;
    gmx_bool          bDoDHDL = FALSE, bDoFEP = FALSE, bDoExpanded = FALSE;
    gmx_bool          do_ene, do_log, do_verbose, bRerunWarnNoV = TRUE,
                      bForceUpdate = FALSE, bCPT;
    gmx_bool          bMasterState;
    int               force_flags, cglo_flags;
    tensor            force_vir, shake_vir, total_vir, tmp_vir, pres;
    int               i, m;
    t_trxstatus      *status;
    rvec              mu_tot;
    t_vcm            *vcm;
    matrix            parrinellorahmanMu, M;
    t_trxframe        rerun_fr;
    gmx_repl_ex_t     repl_ex = nullptr;
    int               nchkpt  = 1;
    gmx_localtop_t   *top;
    t_mdebin         *mdebin   = nullptr;
    gmx_enerdata_t   *enerd;
    PaddedRVecVector  f {};
    gmx_global_stat_t gstat;
    gmx_update_t     *upd   = nullptr;
    t_graph          *graph = nullptr;
    gmx_groups_t     *groups;
    gmx_ekindata_t   *ekind;
    gmx_shellfc_t    *shellfc;
    gmx_bool          bSumEkinhOld, bDoReplEx, bExchanged, bNeedRepartition;
    gmx_bool          bResetCountersHalfMaxH = FALSE;
    gmx_bool          bTemp, bPres, bTrotter;
    real              dvdl_constr;
    rvec             *cbuf        = nullptr;
    int               cbuf_nalloc = 0;
    matrix            lastbox;
    int               lamnew  = 0;
    /* for FEP */
    int               nstfep = 0;
    double            cycles;
    real              saved_conserved_quantity = 0;
    real              last_ekin                = 0;
    t_extmass         MassQ;
    int             **trotter_seq;
    char              sbuf[STEPSTRSIZE], sbuf2[STEPSTRSIZE];
    int               handled_stop_condition = gmx_stop_cond_none; /* compare to get_stop_condition*/


    /* PME load balancing data for GPU kernels */
    pme_load_balancing_t *pme_loadbal      = nullptr;
    gmx_bool              bPMETune         = FALSE;
    gmx_bool              bPMETunePrinting = FALSE;

    /* Interactive MD */
    gmx_bool          bIMDstep = FALSE;

    /* PLUMED */
    int plumedNeedsEnergy=0;
    int plumedWantsToStop=0;
    matrix plumed_vir;
    /* END PLUMED */

#ifdef GMX_FAHCORE
    /* Temporary addition for FAHCORE checkpointing */
    int chkpt_ret;
#endif
    /* Domain decomposition could incorrectly miss a bonded
       interaction, but checking for that requires a global
       communication stage, which does not otherwise happen in DD
       code. So we do that alongside the first global energy reduction
       after a new DD is made. These variables handle whether the
       check happens, and the result it returns. */
    bool              shouldCheckNumberOfBondedInteractions = false;
    int               totalNumberOfBondedInteractions       = -1;

    SimulationSignals signals;
    // Most global communnication stages don't propagate mdrun
    // signals, and will use this object to achieve that.
    SimulationSignaller nullSignaller(nullptr, nullptr, false, false);

    if (!mdrunOptions.writeConfout)
    {
        // This is on by default, and the main known use case for
        // turning it off is for convenience in benchmarking, which is
        // something that should not show up in the general user
        // interface.
        GMX_LOG(mdlog.info).asParagraph().
            appendText("The -noconfout functionality is deprecated, and may be removed in a future version.");
    }
    if (mdrunOptions.timingOptions.resetHalfway)
    {
        GMX_LOG(mdlog.info).asParagraph().
            appendText("The -resethway functionality is deprecated, and may be removed in a future version.");
        if (ir->nsteps > 0)
        {
            /* Signal to reset the counters half the simulation steps. */
            wcycle_set_reset_counters(wcycle, ir->nsteps/2);
        }
        /* Signal to reset the counters halfway the simulation time. */
        bResetCountersHalfMaxH = (mdrunOptions.maximumHoursToRun > 0);
    }

    /* md-vv uses averaged full step velocities for T-control
       md-vv-avek uses averaged half step velocities for T-control (but full step ekin for P control)
       md uses averaged half step kinetic energies to determine temperature unless defined otherwise by GMX_EKIN_AVE_VEL; */
    bTrotter = (EI_VV(ir->eI) && (inputrecNptTrotter(ir) || inputrecNphTrotter(ir) || inputrecNvtTrotter(ir)));

    const gmx_bool bRerunMD      = mdrunOptions.rerun;
    int            nstglobalcomm = mdrunOptions.globalCommunicationInterval;

    if (bRerunMD)
    {
        /* Since we don't know if the frames read are related in any way,
         * rebuild the neighborlist at every step.
         */
        ir->nstlist       = 1;
        ir->nstcalcenergy = 1;
        nstglobalcomm     = 1;
    }

    nstglobalcomm   = check_nstglobalcomm(mdlog, nstglobalcomm, ir);
    bGStatEveryStep = (nstglobalcomm == 1);

    if (bRerunMD)
    {
        ir->nstxout_compressed = 0;
    }
    groups = &top_global->groups;

    gmx_edsam *ed = nullptr;
    if (opt2bSet("-ei", nfile, fnm) || observablesHistory->edsamHistory != nullptr)
    {
        /* Initialize essential dynamics sampling */
        ed = init_edsam(opt2fn_null("-ei", nfile, fnm), opt2fn("-eo", nfile, fnm),
                        top_global,
                        ir, cr, constr,
                        state_global, observablesHistory,
                        oenv, mdrunOptions.continuationOptions.appendFiles);
    }

    if (ir->eSwapCoords != eswapNO)
    {
        /* Initialize ion swapping code */
        init_swapcoords(fplog, ir, opt2fn_master("-swap", nfile, fnm, cr),
                        top_global,
                        state_global, observablesHistory,
                        cr, oenv, mdrunOptions);
    }

    /* Initial values */
    init_md(fplog, cr, outputProvider, ir, oenv, mdrunOptions,
            &t, &t0, state_global, lam0,
            nrnb, top_global, &upd,
            nfile, fnm, &outf, &mdebin,
            force_vir, shake_vir, mu_tot, &bSimAnn, &vcm, wcycle);

    clear_mat(total_vir);
    clear_mat(pres);
    /* Energy terms and groups */
    snew(enerd, 1);
    init_enerdata(top_global->groups.grps[egcENER].nr, ir->fepvals->n_lambda,
                  enerd);

    /* Kinetic energy data */
    snew(ekind, 1);
    init_ekindata(fplog, top_global, &(ir->opts), ekind);
    /* Copy the cos acceleration to the groups struct */
    ekind->cosacc.cos_accel = ir->cos_accel;

    gstat = global_stat_init(ir);

    /* Check for polarizable models and flexible constraints */
    shellfc = init_shell_flexcon(fplog,
                                 top_global, n_flexible_constraints(constr),
                                 ir->nstcalcenergy, DOMAINDECOMP(cr));

    if (shellfc && ir->nstcalcenergy != 1)
    {
        gmx_fatal(FARGS, "You have nstcalcenergy set to a value (%d) that is different from 1.\nThis is not supported in combinations with shell particles.\nPlease make a new tpr file.", ir->nstcalcenergy);
    }
    if (shellfc && DOMAINDECOMP(cr))
    {
        gmx_fatal(FARGS, "Shell particles are not implemented with domain decomposition, use a single rank");
    }
    if (shellfc && ir->bDoAwh)
    {
        gmx_fatal(FARGS, "AWH biasing does not support shell particles.");
    }

    if (inputrecDeform(ir))
    {
        tMPI_Thread_mutex_lock(&deform_init_box_mutex);
        set_deform_reference_box(upd,
                                 deform_init_init_step_tpx,
                                 deform_init_box_tpx);
        tMPI_Thread_mutex_unlock(&deform_init_box_mutex);
    }

    {
        double io = compute_io(ir, top_global->natoms, groups, mdebin->ebin->nener, 1);
        if ((io > 2000) && MASTER(cr))
        {
            fprintf(stderr,
                    "\nWARNING: This run will generate roughly %.0f Mb of data\n\n",
                    io);
        }
    }

    // Local state only becomes valid now.
    std::unique_ptr<t_state> stateInstance;
    t_state *                state;

    if (DOMAINDECOMP(cr))
    {
        top = dd_init_local_top(top_global);

        stateInstance = gmx::compat::make_unique<t_state>();
        state         = stateInstance.get();
        dd_init_local_state(cr->dd, state_global, state);
    }
    else
    {
        state_change_natoms(state_global, state_global->natoms);
        /* We need to allocate one element extra, since we might use
         * (unaligned) 4-wide SIMD loads to access rvec entries.
         */
        f.resize(gmx::paddedRVecVectorSize(state_global->natoms));
        /* Copy the pointer to the global state */
        state = state_global;

        snew(top, 1);
        mdAlgorithmsSetupAtomData(cr, ir, top_global, top, fr,
                                  &graph, mdAtoms, vsite, shellfc);

        update_realloc(upd, state->natoms);
    }

    /* Set up interactive MD (IMD) */
    init_IMD(ir, cr, top_global, fplog, ir->nstcalcenergy, MASTER(cr) ? as_rvec_array(state_global->x.data()) : nullptr,
             nfile, fnm, oenv, mdrunOptions);

    if (DOMAINDECOMP(cr))
    {
        /* Distribute the charge groups over the nodes from the master node */
        dd_partition_system(fplog, ir->init_step, cr, TRUE, 1,
                            state_global, top_global, ir,
                            state, &f, mdAtoms, top, fr,
                            vsite, constr,
                            nrnb, nullptr, FALSE);
        shouldCheckNumberOfBondedInteractions = true;
        update_realloc(upd, state->natoms);
    }

    auto mdatoms = mdAtoms->mdatoms();

    // NOTE: The global state is no longer used at this point.
    // But state_global is still used as temporary storage space for writing
    // the global state to file and potentially for replica exchange.
    // (Global topology should persist.)

    update_mdatoms(mdatoms, state->lambda[efptMASS]);

    const ContinuationOptions &continuationOptions    = mdrunOptions.continuationOptions;
    bool                       startingFromCheckpoint = continuationOptions.startedFromCheckpoint;

    if (ir->bExpanded)
    {
        init_expanded_ensemble(startingFromCheckpoint, ir, state->dfhist);
    }

    if (MASTER(cr))
    {
        if (startingFromCheckpoint)
        {
            /* Update mdebin with energy history if appending to output files */
            if (continuationOptions.appendFiles)
            {
                /* If no history is available (because a checkpoint is from before
                 * it was written) make a new one later, otherwise restore it.
                 */
                if (observablesHistory->energyHistory)
                {
                    restore_energyhistory_from_state(mdebin, observablesHistory->energyHistory.get());
                }
            }
            else if (observablesHistory->energyHistory)
            {
                /* We might have read an energy history from checkpoint.
                 * As we are not appending, we want to restart the statistics.
                 * Free the allocated memory and reset the counts.
                 */
                observablesHistory->energyHistory = {};
            }
        }
        if (!observablesHistory->energyHistory)
        {
            observablesHistory->energyHistory = std::unique_ptr<energyhistory_t>(new energyhistory_t {});
        }
        /* Set the initial energy history in state by updating once */
        update_energyhistory(observablesHistory->energyHistory.get(), mdebin);
    }

    /* Initialize constraints */
    if (constr && !DOMAINDECOMP(cr))
    {
        set_constraints(constr, top, ir, mdatoms, cr);
    }

    /* Initialize AWH and restore state from history in checkpoint if needed. */
    if (ir->bDoAwh)
    {
        ir->awh = new gmx::Awh(fplog, *ir, cr, *ir->awhParams, opt2fn("-awh", nfile, fnm), ir->pull_work);

        if (startingFromCheckpoint)
        {
            /* Restore the AWH history read from checkpoint */
            ir->awh->restoreStateFromHistory(MASTER(cr) ? state_global->awhHistory.get() : nullptr);
        }
        else if (MASTER(cr))
        {
            /* Initialize the AWH history here */
            state_global->awhHistory = ir->awh->initHistoryFromState();
        }
    }

    const bool useReplicaExchange = (replExParams.exchangeInterval > 0);
    if (useReplicaExchange && MASTER(cr))
    {
        repl_ex = init_replica_exchange(fplog, cr->ms, top_global->natoms, ir,
                                        replExParams);
    }

    /* PME tuning is only supported in the Verlet scheme, with PME for
     * Coulomb. It is not supported with only LJ PME, or for
     * reruns. */
    bPMETune = (mdrunOptions.tunePme && EEL_PME(fr->ic->eeltype) && !bRerunMD &&
                !mdrunOptions.reproducible && ir->cutoff_scheme != ecutsGROUP);
    if (bPMETune)
    {
        pme_loadbal_init(&pme_loadbal, cr, mdlog, ir, state->box,
                         fr->ic, fr->nbv->listParams.get(), fr->pmedata, use_GPU(fr->nbv),
                         &bPMETunePrinting);
    }

    if (!ir->bContinuation && !bRerunMD)
    {
        if (state->flags & (1 << estV))
        {
            /* Set the velocities of vsites, shells and frozen atoms to zero */
            for (i = 0; i < mdatoms->homenr; i++)
            {
                if (mdatoms->ptype[i] == eptVSite ||
                    mdatoms->ptype[i] == eptShell)
                {
                    clear_rvec(state->v[i]);
                }
                else if (mdatoms->cFREEZE)
                {
                    for (m = 0; m < DIM; m++)
                    {
                        if (ir->opts.nFreeze[mdatoms->cFREEZE[i]][m])
                        {
                            state->v[i][m] = 0;
                        }
                    }
                }
            }
        }

        if (constr)
        {
            /* Constrain the initial coordinates and velocities */
            do_constrain_first(fplog, constr, ir, mdatoms, state,
                               cr, nrnb, fr, top);
        }
        if (vsite)
        {
            /* Construct the virtual sites for the initial configuration */
            construct_vsites(vsite, as_rvec_array(state->x.data()), ir->delta_t, nullptr,
                             top->idef.iparams, top->idef.il,
                             fr->ePBC, fr->bMolPBC, cr, state->box);
        }
    }

    if (ir->efep != efepNO)
    {
        /* Set free energy calculation frequency as the greatest common
         * denominator of nstdhdl and repl_ex_nst. */
        nstfep = ir->fepvals->nstdhdl;
        if (ir->bExpanded)
        {
            nstfep = gmx_greatest_common_divisor(ir->expandedvals->nstexpanded, nstfep);
        }
        if (useReplicaExchange)
        {
            nstfep = gmx_greatest_common_divisor(replExParams.exchangeInterval, nstfep);
        }
    }

    /* Be REALLY careful about what flags you set here. You CANNOT assume
     * this is the first step, since we might be restarting from a checkpoint,
     * and in that case we should not do any modifications to the state.
     */
    bStopCM = (ir->comm_mode != ecmNO && !ir->bContinuation);

    if (continuationOptions.haveReadEkin)
    {
        restore_ekinstate_from_state(cr, ekind, &state_global->ekinstate);
    }

    cglo_flags = (CGLO_INITIALIZATION | CGLO_TEMPERATURE | CGLO_GSTAT
                  | (EI_VV(ir->eI) ? CGLO_PRESSURE : 0)
                  | (EI_VV(ir->eI) ? CGLO_CONSTRAINT : 0)
                  | (continuationOptions.haveReadEkin ? CGLO_READEKIN : 0));

    bSumEkinhOld = FALSE;
    /* To minimize communication, compute_globals computes the COM velocity
     * and the kinetic energy for the velocities without COM motion removed.
     * Thus to get the kinetic energy without the COM contribution, we need
     * to call compute_globals twice.
     */
    for (int cgloIteration = 0; cgloIteration < (bStopCM ? 2 : 1); cgloIteration++)
    {
        int cglo_flags_iteration = cglo_flags;
        if (bStopCM && cgloIteration == 0)
        {
            cglo_flags_iteration |= CGLO_STOPCM;
            cglo_flags_iteration &= ~CGLO_TEMPERATURE;
        }
        compute_globals(fplog, gstat, cr, ir, fr, ekind, state, mdatoms, nrnb, vcm,
                        nullptr, enerd, force_vir, shake_vir, total_vir, pres, mu_tot,
                        constr, &nullSignaller, state->box,
                        &totalNumberOfBondedInteractions, &bSumEkinhOld, cglo_flags_iteration
                        | (shouldCheckNumberOfBondedInteractions ? CGLO_CHECK_NUMBER_OF_BONDED_INTERACTIONS : 0));
    }
    checkNumberOfBondedInteractions(fplog, cr, totalNumberOfBondedInteractions,
                                    top_global, top, state,
                                    &shouldCheckNumberOfBondedInteractions);
    if (ir->eI == eiVVAK)
    {
        /* a second call to get the half step temperature initialized as well */
        /* we do the same call as above, but turn the pressure off -- internally to
           compute_globals, this is recognized as a velocity verlet half-step
           kinetic energy calculation.  This minimized excess variables, but
           perhaps loses some logic?*/

        compute_globals(fplog, gstat, cr, ir, fr, ekind, state, mdatoms, nrnb, vcm,
                        nullptr, enerd, force_vir, shake_vir, total_vir, pres, mu_tot,
                        constr, &nullSignaller, state->box,
                        nullptr, &bSumEkinhOld,
                        cglo_flags & ~CGLO_PRESSURE);
    }

    /* Calculate the initial half step temperature, and save the ekinh_old */
    if (!continuationOptions.startedFromCheckpoint)
    {
        for (i = 0; (i < ir->opts.ngtc); i++)
        {
            copy_mat(ekind->tcstat[i].ekinh, ekind->tcstat[i].ekinh_old);
        }
    }

    /* need to make an initiation call to get the Trotter variables set, as well as other constants for non-trotter
       temperature control */
    trotter_seq = init_npt_vars(ir, state, &MassQ, bTrotter);

    if (MASTER(cr))
    {
        if (!ir->bContinuation)
        {
            if (constr && ir->eConstrAlg == econtLINCS)
            {
                fprintf(fplog,
                        "RMS relative constraint deviation after constraining: %.2e\n",
                        constr_rmsd(constr));
            }
            if (EI_STATE_VELOCITY(ir->eI))
            {
                real temp = enerd->term[F_TEMP];
                if (ir->eI != eiVV)
                {
                    /* Result of Ekin averaged over velocities of -half
                     * and +half step, while we only have -half step here.
                     */
                    temp *= 2;
                }
                fprintf(fplog, "Initial temperature: %g K\n", temp);
            }
        }

        if (bRerunMD)
        {
            fprintf(stderr, "starting md rerun '%s', reading coordinates from"
                    " input trajectory '%s'\n\n",
                    *(top_global->name), opt2fn("-rerun", nfile, fnm));
            if (mdrunOptions.verbose)
            {
                fprintf(stderr, "Calculated time to finish depends on nsteps from "
                        "run input file,\nwhich may not correspond to the time "
                        "needed to process input trajectory.\n\n");
            }
        }
        else
        {
            char tbuf[20];
            fprintf(stderr, "starting mdrun '%s'\n",
                    *(top_global->name));
            if (ir->nsteps >= 0)
            {
                sprintf(tbuf, "%8.1f", (ir->init_step+ir->nsteps)*ir->delta_t);
            }
            else
            {
                sprintf(tbuf, "%s", "infinite");
            }
            if (ir->init_step > 0)
            {
                fprintf(stderr, "%s steps, %s ps (continuing from step %s, %8.1f ps).\n",
                        gmx_step_str(ir->init_step+ir->nsteps, sbuf), tbuf,
                        gmx_step_str(ir->init_step, sbuf2),
                        ir->init_step*ir->delta_t);
            }
            else
            {
                fprintf(stderr, "%s steps, %s ps.\n",
                        gmx_step_str(ir->nsteps, sbuf), tbuf);
            }
        }
        fprintf(fplog, "\n");
    }

    /* PLUMED */
    if(plumedswitch){
      /* detect plumed API version */
      int pversion=0;
      plumed_cmd(plumedmain,"getApiVersion",&pversion);
      /* setting kbT is only implemented with api>1) */
      real kbT=ir->opts.ref_t[0]*BOLTZ;
      if(pversion>1) plumed_cmd(plumedmain,"setKbT",&kbT);
      if(pversion>2){
        int res=1;
        if( (continuationOptions.startedFromCheckpoint) ) plumed_cmd(plumedmain,"setRestart",&res);
      }

      if(cr->ms && cr->ms->nsim>1) {
        if(MASTER(cr)) plumed_cmd(plumedmain,"GREX setMPIIntercomm",&cr->ms->mpi_comm_masters);
        if(PAR(cr)){
          if(DOMAINDECOMP(cr)) {
            plumed_cmd(plumedmain,"GREX setMPIIntracomm",&cr->dd->mpi_comm_all);
          }else{
            plumed_cmd(plumedmain,"GREX setMPIIntracomm",&cr->mpi_comm_mysim);
          }
        }
        plumed_cmd(plumedmain,"GREX init",NULL);
      }
      if(PAR(cr)){
        if(DOMAINDECOMP(cr)) {
          plumed_cmd(plumedmain,"setMPIComm",&cr->dd->mpi_comm_all);
        }
      }
      plumed_cmd(plumedmain,"setNatoms",&top_global->natoms);
      plumed_cmd(plumedmain,"setMDEngine","gromacs");
      plumed_cmd(plumedmain,"setLog",fplog);
      real real_delta_t=ir->delta_t;
      plumed_cmd(plumedmain,"setTimestep",&real_delta_t);
      plumed_cmd(plumedmain,"init",NULL);

      if(PAR(cr)){
        if(DOMAINDECOMP(cr)) {
          plumed_cmd(plumedmain,"setAtomsNlocal",&cr->dd->nat_home);
          plumed_cmd(plumedmain,"setAtomsGatindex",cr->dd->gatindex);
        }
      }
    }
    /* END PLUMED */

    walltime_accounting_start(walltime_accounting);
    wallcycle_start(wcycle, ewcRUN);
    print_start(fplog, cr, walltime_accounting, "mdrun");

    /* safest point to do file checkpointing is here.  More general point would be immediately before integrator call */
#ifdef GMX_FAHCORE
    chkpt_ret = fcCheckPointParallel( cr->nodeid,
                                      NULL, 0);
    if (chkpt_ret == 0)
    {
        gmx_fatal( 3, __FILE__, __LINE__, "Checkpoint error on step %d\n", 0 );
    }
#endif

    /***********************************************************
     *
     *             Loop over MD steps
     *
     ************************************************************/

    /* if rerunMD then read coordinates and velocities from input trajectory */
    if (bRerunMD)
    {
        if (getenv("GMX_FORCE_UPDATE"))
        {
            bForceUpdate = TRUE;
        }

        rerun_fr.natoms = 0;
        if (MASTER(cr))
        {
            bLastStep = !read_first_frame(oenv, &status,
                                          opt2fn("-rerun", nfile, fnm),
                                          &rerun_fr, TRX_NEED_X | TRX_READ_V);
            if (rerun_fr.natoms != top_global->natoms)
            {
                gmx_fatal(FARGS,
                          "Number of atoms in trajectory (%d) does not match the "
                          "run input file (%d)\n",
                          rerun_fr.natoms, top_global->natoms);
            }
            if (ir->ePBC != epbcNONE)
            {
                if (!rerun_fr.bBox)
                {
                    gmx_fatal(FARGS, "Rerun trajectory frame step %d time %f does not contain a box, while pbc is used", rerun_fr.step, rerun_fr.time);
                }
                if (max_cutoff2(ir->ePBC, rerun_fr.box) < gmx::square(fr->rlist))
                {
                    gmx_fatal(FARGS, "Rerun trajectory frame step %d time %f has too small box dimensions", rerun_fr.step, rerun_fr.time);
                }
            }
        }

        if (PAR(cr))
        {
            rerun_parallel_comm(cr, &rerun_fr, &bLastStep);
        }

        if (ir->ePBC != epbcNONE)
        {
            /* Set the shift vectors.
             * Necessary here when have a static box different from the tpr box.
             */
            calc_shifts(rerun_fr.box, fr->shift_vec);
        }
    }

    /* Loop over MD steps or if rerunMD to end of input trajectory,
     * or, if max_hours>0, until max_hours is reached.
     */
    real max_hours   = mdrunOptions.maximumHoursToRun;
    bFirstStep       = TRUE;
    /* Skip the first Nose-Hoover integration when we get the state from tpx */
    bInitStep        = !startingFromCheckpoint || EI_VV(ir->eI);
    bSumEkinhOld     = FALSE;
    bExchanged       = FALSE;
    bNeedRepartition = FALSE;