Residence time

.devcontainer/Dockerfile

@@ -1,19 +1,52 @@
-ARG VARIANT=ubuntu-22.04
-FROM mcr.microsoft.com/vscode/devcontainers/cpp:0-${VARIANT}
+ARG CUDA_VERSION=12.3.2
+ARG OS_VERSION=ubuntu22.04
+
+FROM nvcr.io/nvidia/cuda:${CUDA_VERSION}-devel-${OS_VERSION}
 
 LABEL maintainer="Bernd Doser <[email protected]>"
 
 RUN apt-get update \
  && export DEBIAN_FRONTEND=noninteractive \
  && apt-get -y install --no-install-recommends \
+       clang \
+       gdb \
+       git \
        libomp-14-dev \
+       python3 \
+       python3-dev \
+       python3-pip \
        python3-pip \
+       python3-venv \
+       sudo \
+       vim \
  && apt-get clean \
  && rm -rf /var/lib/apt/lists/*
 
 RUN pip install --upgrade pip \
  && hash -r pip3
 
 RUN pip install \
+      cmake \
       dash \
       pandas
+
+ARG USERNAME=vscode
+ARG USER_UID=15005
+ARG USER_GID=15000
+
+# Create the user
+RUN groupadd --gid $USER_GID $USERNAME \
+    && useradd --uid $USER_UID --gid $USER_GID -m $USERNAME \
+    #
+    # [Optional] Add sudo support. Omit if you don't need to install software after connecting.
+    && apt-get update \
+    && apt-get install -y sudo \
+    && echo $USERNAME ALL=\(root\) NOPASSWD:ALL > /etc/sudoers.d/$USERNAME \
+    && chmod 0440 /etc/sudoers.d/$USERNAME
+
+# ********************************************************
+# * Anything else you want to do like clean up goes here *
+# ********************************************************
+
+# [Optional] Set the default user. Omit if you want to keep the default as root.
+USER $USERNAME

.devcontainer/devcontainer.json

@@ -4,8 +4,10 @@
 		"dockerfile": "Dockerfile"
 	},
     "runArgs": [
-        "--cap-add=SYS_PTRACE",
-        "--security-opt", "seccomp=unconfined"
+		"--gpus=all",
+		"--cap-add=SYS_PTRACE",
+		"--security-opt",
+		"seccomp=unconfined"
     ],
 
     // Add the IDs of extensions you want installed when the container is created.
@@ -30,7 +32,8 @@
     // Comment out connect as root instead. More info: https://aka.ms/vscode-remote/containers/non-root.
     "remoteUser": "vscode",
 
+    // Mount external data volume for debugging purposes
     "mounts": [
-        "source=${localEnv:HOME}/data/gromacs-ramd,target=/data,type=bind,consistency=cached"
+        "source=/home/doserbd/data/gromacs-ramd,target=/data,type=bind,consistency=cached"
     ]
 }

.vscode/launch.json

@@ -216,6 +216,30 @@
                 }
             ]
         },
+        {
+            "name": "(gdb) 4water grompp ramd",
+            "type": "cppdbg",
+            "request": "launch",
+            "program": "${workspaceFolder}/build/bin/gmx",
+            "args": ["grompp",
+                     "-f", "${workspaceFolder}/src/gromacs/ramd/tests/data/4water/4water.mdp",
+                     "-c", "${workspaceFolder}/src/gromacs/ramd/tests/data/4water/4water.gro",
+                     "-p", "${workspaceFolder}/src/gromacs/ramd/tests/data/4water/4water.top",
+                     "-n", "${workspaceFolder}/src/gromacs/ramd/tests/data/4water/4water2.ndx",
+                     "-o", "topol.tpr"],
+            "stopAtEntry": false,
+            "cwd": "${workspaceFolder}/build/tests",
+            "environment": [],
+            "externalConsole": false,
+            "MIMode": "gdb",
+            "setupCommands": [
+                {
+                    "description": "Enable pretty-printing for gdb",
+                    "text": "-enable-pretty-printing",
+                    "ignoreFailures": true
+                }
+            ]
+        },
         {
             "name": "(gdb) mdrun",
             "type": "cppdbg",
@@ -377,7 +401,8 @@
             "type": "cppdbg",
             "request": "launch",
             "program": "${workspaceFolder}/build/bin/ramd-test",
-            "args": [],
+            // "args": ["--gtest_filter=RAMDTest.CalculateForces1WDHI"],
+            // "args": ["--gtest_filter=RAMDTest.binding_residues"],
             "stopAtEntry": false,
             "cwd": "${workspaceFolder}/build/tests",
             "environment": [],

.vscode/settings.json

@@ -1,6 +1,7 @@
 {
     "cmake.configureSettings": {
-        "GMX_BUILD_OWN_FFTW": "ON"
+        "GMX_BUILD_OWN_FFTW": "ON",
+        "GMX_GPU": "CUDA"
     },
     "cmake.generator": "Unix Makefiles",
     "clang-format.executable": "/usr/bin/clang-format-7",

README.md

@@ -60,7 +60,7 @@ Please use following mdp options:
 
    This parameter affect absolute dissociation time but have less
    effect on the relative dissociation times of different compounds. It is
-   recommended to use default value.
+   recommended to use default value. Default value is 0.0025 nm.
 
  * ramd-group1-max-dist
 
@@ -72,7 +72,7 @@ Please use following mdp options:
    upper limit of this parameter since motion of the free ligand due to the
    external force is very fast (i.e. the last part of the trajectory, where the
    ligand does not interact with the protein, usually has a negligible contribution
-   to the observed dissociation time).
+   to the observed dissociation time). Default value is 4 nm.
 
  * ramd-group1-receptor
 
@@ -105,3 +105,13 @@ Please use following mdp options:
    Each ligand is subject to a RAMD force until the individual ligand has left the
    dissociation radius. The simulation stops when all ligands have left the
    dissociation radius. Default value is 'yes'.
+
+ * ramd-use-residence-dist
+
+   If 'yes', the residence time will be printed to the log file.
+   Default value is 'no'.
+
+ * ramd-residence-dist
+
+   Residence distance in nm. If the ligand is within this distance from the receptor, it is considered to be bound.
+   Default value is 0.55 nm.

src/gromacs/fileio/tpxio.cpp

@@ -1518,18 +1518,23 @@ static void do_inputrec(gmx::ISerializer* serializer, t_inputrec* ir, int file_v
                 serializer->doInt(&ir->ramdParams->ngroup);
                 if (serializer->reading())
                 {
-                    snew(ir->ramdParams->group, ir->ramdParams->ngroup);
+                    ir->ramdParams->group.resize(ir->ramdParams->ngroup);
                 }
                 for (int g = 0; g < ir->ramdParams->ngroup; g++)
                 {
                     serializer->doReal(&ir->ramdParams->group[g].force);
                     serializer->doReal(&ir->ramdParams->group[g].max_dist);
                     serializer->doReal(&ir->ramdParams->group[g].r_min_dist);
+                    serializer->doString(&ir->ramdParams->group[g].bind_res_receptor);
+                    serializer->doString(&ir->ramdParams->group[g].bind_res_ligand);
+
                 }
                 serializer->doInt(&ir->ramdParams->eval_freq);
                 serializer->doInt(&ir->ramdParams->force_out_freq);
                 serializer->doBool(&ir->ramdParams->old_angle_dist);
                 serializer->doBool(&ir->ramdParams->connected_ligands);
+                serializer->doBool(&ir->ramdParams->use_residence_dist);
+                serializer->doReal(&ir->ramdParams->residence_dist);
             }
         }
     }

src/gromacs/gmxpreprocess/readir.cpp

@@ -3127,6 +3127,18 @@ void get_ir(const char*     mdparin,
     sfree(dumstr[1]);
 }
 
+bool groupExists(const std::string& s, gmx::ArrayRef<const IndexGroup> indexGroups)
+{
+    for (int i = 0; i < gmx::ssize(indexGroups); i++)
+    {
+        if (gmx_strcasecmp(s.c_str(), indexGroups[i].name.c_str()) == 0)
+        {
+            return true;
+        }
+    }
+    return false;
+}
+
 int getGroupIndex(const std::string& s, gmx::ArrayRef<const IndexGroup> indexGroups)
 {
     for (int i = 0; i < gmx::ssize(indexGroups); i++)
@@ -4267,6 +4279,11 @@ void do_index(const char*                    mdparin,
         }
     }
 
+    if (ir->bRAMD && ir->ramdParams->use_residence_dist)
+    {
+        add_residence_time_groups(ir, defaultIndexGroups, inputrecStrings->pullGroupNames);
+    }
+
     if (ir->bPull || ir->bRAMD)
     {
         for (int i = 1; i < ir->pull->ngroup; i++)

src/gromacs/gmxpreprocess/readir.h

@@ -121,6 +121,9 @@ void check_ir(const char*                    mdparin,
               t_gromppopts*                  opts,
               WarningHandler*                wi);
 
+//! Returns true if string \p s is in \p indexGroups
+bool groupExists(const std::string& s, gmx::ArrayRef<const IndexGroup> indexGroups);
+
 //! Returns the index of string \p s in \p indexGroups or exit with a verbose fatal error when not found
 int getGroupIndex(const std::string& s, gmx::ArrayRef<const IndexGroup> indexGroups);
 
@@ -181,6 +184,9 @@ pull_t* set_pull_init(t_inputrec*                    ir,
 void read_ramdparams(std::vector<t_inpfile>* inp, gmx::RAMDParams* ramdparams, WarningHandler* wi);
 /* Reads the ramd parameters, returns a list of the ramd group names */
 
+void add_residence_time_groups(t_inputrec* ir, std::vector<IndexGroup> defaultIndexGroups,
+    std::vector<std::string>& pullGroupNames);
+
 std::vector<std::string> read_rotparams(std::vector<t_inpfile>* inp, t_rot* rot, WarningHandler* wi);
 /* Reads enforced rotation parameters, returns a list of the rot group names */
 

src/gromacs/gmxpreprocess/readramd.cpp

@@ -38,6 +38,8 @@
 #include "gromacs/gmxpreprocess/readir.h"
 #include "gromacs/mdtypes/inputrec.h"
 #include "gromacs/mdtypes/ramd_params.h"
+#include "gromacs/mdtypes/pull_params.h"
+#include "gromacs/topology/index.h"
 #include "gromacs/topology/topology.h"
 #include "gromacs/utility/cstringutil.h"
 #include "gromacs/utility/smalloc.h"
@@ -46,11 +48,10 @@ void read_ramdparams(std::vector<t_inpfile>* inp, gmx::RAMDParams* ramdparams, W
 {
     ramdparams->seed = get_eint(inp, "ramd-seed", 1234, wi);
     ramdparams->ngroup = get_eint(inp, "ramd-ngroups", 1, wi);
-    snew(ramdparams->group, ramdparams->ngroup);
 
     for (int i = 0; i < ramdparams->ngroup; i++)
     {
-        auto ramdgrp = &ramdparams->group[i];
+        gmx::RAMDGroup ramdgrp;
         auto ramd_prefix = std::string("ramd-group") + std::to_string(i + 1);
         auto pull1_prefix = std::string("pull-group") + std::to_string(i * 2 + 1);
         auto pull2_prefix = std::string("pull-group") + std::to_string(i * 2 + 2);
@@ -65,9 +66,13 @@ void read_ramdparams(std::vector<t_inpfile>* inp, gmx::RAMDParams* ramdparams, W
         inp->emplace_back(0, 1, false, false, false, pull2_prefix + "-pbcatom",
             get_estr(inp, ramd_prefix + "-ligand-pbcatom", "0"));
 
-        ramdgrp->force = get_ereal(inp, ramd_prefix + "-force", 600, wi);
-        ramdgrp->r_min_dist = get_ereal(inp, ramd_prefix + "-r-min-dist", 0.0025, wi);
-        ramdgrp->max_dist  = get_ereal(inp, ramd_prefix + "-max-dist", 4.0, wi);
+        ramdgrp.force = get_ereal(inp, ramd_prefix + "-force", 600, wi);
+        ramdgrp.r_min_dist = get_ereal(inp, ramd_prefix + "-r-min-dist", 0.0025, wi);
+        ramdgrp.max_dist = get_ereal(inp, ramd_prefix + "-max-dist", 4.0, wi);
+        ramdgrp.bind_res_receptor = get_estr(inp, ramd_prefix + "-receptor-res", "receptor");
+        ramdgrp.bind_res_ligand = get_estr(inp, ramd_prefix + "-ligand-res", "ligand");
+
+        ramdparams->group.emplace_back(ramdgrp);
     }
 
     inp->emplace_back(0, 1, false, false, false, "pull-pbc-ref-prev-step-com",
@@ -106,4 +111,55 @@ void read_ramdparams(std::vector<t_inpfile>* inp, gmx::RAMDParams* ramdparams, W
     }
 
     ramdparams->connected_ligands = getEnum<Boolean>(inp, "ramd-connected-ligands", wi) != Boolean::No;
+    ramdparams->use_residence_dist = getEnum<Boolean>(inp, "ramd-use-residence-dist", wi) != Boolean::No;
+    ramdparams->residence_dist = get_ereal(inp, "ramd-residence-dist", 0.55, wi);
+}
+
+
+void add_residence_time_groups(t_inputrec* ir, std::vector<IndexGroup> indexGroups,
+    std::vector<std::string>& pullGroupNames)
+{
+    std::string receptor = ir->ramdParams->group[0].bind_res_receptor;
+    std::string ligand = ir->ramdParams->group[0].bind_res_ligand;
+
+    int nb_bind_res_receptor = 0;
+    int nb_bind_res_ligand = 0;
+    for (int i = 0; i < gmx::ssize(indexGroups); i++)
+    {
+        if (gmx_wcmatch((receptor + "_group*").c_str(), indexGroups[i].name.c_str()) == 0)
+        {
+            ++nb_bind_res_receptor;
+        }
+        if (gmx_wcmatch((ligand + "_group*").c_str(), indexGroups[i].name.c_str()) == 0)
+        {
+            ++nb_bind_res_ligand;
+        }
+    }
+
+    GMX_ASSERT(nb_bind_res_receptor == nb_bind_res_ligand, "Number of receptor binding groups must be equal to number of ligand binding groups.");
+
+    for (int i = 0; i < nb_bind_res_receptor; ++i)
+    {
+        std::string receptor_group_string = receptor + "_group_" + std::to_string(i + 1);
+        pullGroupNames.push_back(receptor_group_string);
+        if (groupExists(receptor_group_string, indexGroups)) {
+            const int receptor_gid = getGroupIndex(receptor_group_string.c_str(), indexGroups);
+            t_pull_group receptor_group;
+            receptor_group.ind = indexGroups[receptor_gid].particleIndices;
+            receptor_group.pbcatom = 0;
+            ir->pull->group.push_back(receptor_group);
+            ir->pull->ngroup++;
+        }
+
+        std::string ligand_group_string = ligand + "_group_" + std::to_string(i + 1);
+        pullGroupNames.push_back(ligand_group_string);
+        if (groupExists(ligand_group_string, indexGroups)) {
+            const int ligand_gid = getGroupIndex(ligand_group_string.c_str(), indexGroups);
+            t_pull_group ligand_group;
+            ligand_group.ind = indexGroups[ligand_gid].particleIndices;
+            ligand_group.pbcatom = 0;
+            ir->pull->group.push_back(ligand_group);
+            ir->pull->ngroup++;
+        }
+    }
 }

src/gromacs/mdrun/md.cpp

@@ -514,6 +514,14 @@ void gmx::LegacySimulator::do_md()
     {
         EnergyData::initializeEnergyHistory(startingBehavior_, observablesHistory_, &energyOutput);
     }
+
+    /* RAMD */
+    std::unique_ptr<RAMD> ramd = nullptr;
+    if (ir->bRAMD)
+    {
+        ramd = std::make_unique<RAMD>(*ir->ramdParams, pullWork_, startingBehavior_, cr_, nFile_, fnm_, oenv_, fpLog_);
+        fr_->forceProviders->addForceProvider(ramd.get());
+    }
 
     preparePrevStepPullCom(
             ir, pullWork_, md->massT, state_, stateGlobal_, cr_, startingBehavior_ != StartingBehavior::NewSimulation);
@@ -626,14 +634,6 @@ void gmx::LegacySimulator::do_md()
     int64_t step     = ir->init_step;
     int64_t step_rel = 0;
 
-    /* RAMD */
-    std::unique_ptr<RAMD> ramd = nullptr;
-    if (ir->bRAMD)
-    {
-        ramd = std::make_unique<RAMD>(*ir->ramdParams, pullWork_, startingBehavior_, cr_, nFile_, fnm_, oenv_, fpLog_);
-        fr_->forceProviders->addForceProvider(ramd.get());
-    }
-
     /* 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

src/gromacs/mdtypes/inputrec.cpp

@@ -640,6 +640,8 @@ static void pr_ramd_group(FILE* fp, int indent, int g, const gmx::RAMDGroup grp)
     PR("force", grp.force);
     PR("max_dist", grp.max_dist);
     PR("r_min_dist", grp.r_min_dist);
+    PS("bind_res_receptor", grp.bind_res_receptor.c_str());
+    PS("bind_res_ligand", grp.bind_res_ligand.c_str());
 }
 
 static void pr_ramd(FILE* fp, int indent, const gmx::RAMDParams ramd)
@@ -654,6 +656,8 @@ static void pr_ramd(FILE* fp, int indent, const gmx::RAMDParams ramd)
     PI("ramd-force-out-freq", ramd.force_out_freq);
     PS("ramd-old-angle-dist", EBOOL(ramd.old_angle_dist));
     PS("ramd-connected-ligands", EBOOL(ramd.connected_ligands));
+    PS("ramd-use-residence-dist", EBOOL(ramd.use_residence_dist));
+    PR("ramd-residence-dist", ramd.residence_dist);
 }
 
 static void pr_awh_bias_dim(FILE* fp, int indent, const gmx::AwhDimParams& awhDimParams, const char* prefix)