GROMACS FMM & Constant pH

https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph
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Documentation and tutorials for GROMACS Fast Multipole Method (FMM) and Constant pH MD code, a fork...
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### Successful build output example

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/docs/install_guide

Example output indicating a successful compilation of the gmx executable.

```text
[100%] Linking CXX executable ../../bin/gmx
[100%] Built target gmx

```

--------------------------------

### Example output of verification command

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/docs/install_guide

Example output from the verification command, showing the executable path and available options, including '-ldhis'.

```text
       :-) GROMACS - gmx pdb2gmx, 2024-dev-20240108-249226c0e2-local (-:)

Executable:   /home/ebriand/Projects/gromacs_juelich/cmake-build-relwithdebinfo_localsettings/bin/gmx
Data prefix:  /home/ebriand/Projects/gromacs_juelich (source tree)
Working dir:  /home/ebriand/Projects/__CPH_Runs/SimpleLambdadyn/structure_qihi/single_glu_qi
Command line:
  gmx pdb2gmx -h

            [-[no]ldglu] [-[no]ldhis] [-[no]ldasp] [-[no]ldlys] [-[no]ldtyr]

GROMACS reminds you: "Life in the streets is not easy" (Marky Mark)

 -[no]ldhis                 (no)

```

--------------------------------

### Create build directory

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/docs/install_guide

Creates a separate directory for building the code and navigates into it.

```bash
mkdir build
cd build

```

--------------------------------

### Set up alias for gmx

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/docs/install_guide

Sets up an alias for the gmx executable, pointing to the installed constant pH build.

```bash
alias gmx=/directory/where/gromacs-constantph-installed/bin/gmx
```

--------------------------------

### Configure the build with CMake

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/docs/install_guide

Configures the build process using CMake with specific options for FMM and constant pH.

```bash
cmake -DCMAKE_BUILD_TYPE=Release \
      -DGMX_BUILD_OWN_FFTW=ON \
      -DGMX_GPU=CUDA \
      -DCUDA_TOOLKIT_ROOT_DIR=/usr/local/cuda-11.1 \
      -DGMX_SIMD=AUTO \
      -DGMX_WITH_FMM=ON \
      -DGMX_CONSTANTPH=ON \
      $CPHSOURCEDIR

```

--------------------------------

### Verify gmx binary installation

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/docs/install_guide

Verifies that the correct gmx binary is in the PATH by checking its help output for the 'ldhis' option.

```bash
gmx pdb2gmx -h | grep ldhis
```

--------------------------------

### Clone the FMM repository

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/docs/install_guide

Clones the FMM repository from MPCDF GitLab.

```bash
git clone https://gitlab.mpcdf.mpg.de/grubmueller/fmm.git

```

--------------------------------

### Switch to the constant pH simulation branch

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/docs/install_guide

Switches the cloned repository to the stable branch for constant pH simulations.

```bash
git checkout constant_ph_stable

```

--------------------------------

### Example Runfile Configuration

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/docs/tutorials/cph-titration

A sample YAML configuration file for constant pH titration simulations, outlining various parameters for simulation control, input files, system setup, and launch settings.

```yaml
---
 runfileVersion: 3
 runcontrol:
    replicaNumber: 7
    lambdaEquilRunDuration: 0.1
    structureEquilRunDuration: 1
    productionRunDuration: 2
    runDir: "/lys2/"
 inputFiles:
    templateDirectory: "template_c36m"
    inputPdb: "lysozyme.pdb"
    customLdpFile: ""
    genionMDPTemplate: "genion.mdp.template"
    emMDPTemplate: "em.mdp.template"
    lambdaEquilMDPTemplate: "lambdaequil_coupled.mdp.template"
    structureEquilMDPTemplate: "structureequil_coupled.mdp.template"
    productionMDPTemplate: "titration_coupled.mdp.template"
    indexFile: ""
 systemParameters:
    boxVector: 8.0
    fmmDepth: 2
    velgenSeedBaseValue: 84521
    waterModel: "tip3p"
    prepfilesAdditionalCommands:
        - "ln -s /home/ebriand/Projects/__CPH_FF/charmm36m-lambdadyn.ff/"
    ffName: "charmm36m-lambdadyn"
    pdb2gmxAdditionalArguments: " -ignh -ldglu -ldhis -ldasp "
    sodiumName: "SOD"
    chlorideName: "CLA"
    keepawayGroup: "C-alpha"
    distResidueToBuffer: 3.0
    distProteinToBuffer: 2.0
    distBufferTolerance: 0.3
    ionConcentration: 0.150
 titration:
    phValues: [-1.0, -0.5, 0.0, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, 8.0, 8.5, 9.0]
    mainRunBarrier: 6.0
    nstlambdaout: 250
 localGromacsLaunch:
    gromppThreads: 4
    localGromacsBinary: "/home/ebriand/Projects/gromacs_publication_builds/stable/stable_v1/bin/gmx"
 clusterJobLaunch:
    jobPrefix: "LYZ_2"
    clusterLoginNode: "moa1"
    clusterGromacsGMXRC: "/home/ebriand/Projects/gromacs_publication_builds/stable/cluster/stable_v1/bin/GMXRC"

```

--------------------------------

### Compile the gmx executable

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/docs/install_guide

Compiles the gmx executable using make, utilizing 8 threads for the build process.

```bash
make -j8 gmx

```

--------------------------------

### Initial Setup (Generally not used)

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/docs/tutorials/cph-titration

This command is typically not used directly for the main simulation flow but might be part of initial setup or testing.

```bash
python titrate_v3.py replica -r lyzozyme_1.yaml
```

--------------------------------

### Lambda equilibration output example

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/docs/tutorials/cph-lysozyme-tuto

Example output from lambda equilibration, showing lambda values and velocities for residues.

```text
;     residue [   4]  lambda_p =        -0.0319707729   velocity =         -0.1973873526
;                     lambda_t =        -0.0541575402   velocity =          0.0518201627
;     residue [   5]  lambda_p =         0.0274856947   velocity =          0.1474107057
;                     lambda_t =         0.6484327912   velocity =          0.0308893304
;     residue [   6]  lambda_p =        -0.0059586708   velocity =         -0.0520664826
;                     lambda_t =         0.3720209897   velocity =         -0.1076164022
;     residue [   7]  lambda_p =        -0.0092997942   velocity =         -0.0363448523
;                     lambda_t =         0.0587233007   velocity =         -0.1340652406
;     residue [   8]  lambda_p =         1.1058342457   velocity =         -0.1004268229
;                     lambda_t =         0.2853246629   velocity =         -0.1654260606
;     residue [   9]  lambda_p =        -0.0331853665   velocity =          0.2384097874
;                     lambda_t =         0.1017527282   velocity =         -0.0818591341
; Writing buffer checkpoint:
;      collective buffer lambda         0.0000000000 (v:         0.0000000000  F_(t-1)         0.0000000000)
; closing output file...

```

--------------------------------

### Source GMXRC script

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/docs/install_guide

Sources the GMXRC script to set up the environment for the GROMACS constant pH build.

```bash
source /directory/where/gromacs-constantph-installed/bin/GMXRC
```

--------------------------------

### TI and Calibration Example

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/docs/cph/cph_parameters

Example parameters for TI (Thermodynamic Integration) and calibration-related settings.

```properties
constantph-ti-axis = GLUL0002 p BufWater0001 buffer
constantph-ti-delta-lambda = 0.0 0.0
constantph-disabled-buffers = all   
constantph-ti-delay-steps = 0
```

--------------------------------

### Runfile Example

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/docs/cph/titration_script

A complete runfile example in YAML format with all required parameters for a titration simulation workflow.

```yaml
---
runfileVersion: 3
runcontrol:
   replicaNumber: 7
   lambdaEquilRunDuration: 0.1
   structureEquilRunDuration: 1
   productionRunDuration: 2
   runDir: "/lys2/"
inputFiles:
   templateDirectory: "template_c36m"
   inputPdb: "lyzozyme.pdb"
   customLdpFile: ""
   genionMDPTemplate: "genion.mdp.template"
   emMDPTemplate: "em.mdp.template"
   lambdaEquilMDPTemplate: "lambdaequil_coupled.mdp.template"
   structureEquilMDPTemplate: "structureequil_coupled.mdp.template"
   productionMDPTemplate: "titration_coupled.mdp.template"
systemParameters:
   boxVector: 8.0
   fmmDepth: 2
   velgenSeedBaseValue: 84521
   waterModel: "tip3p"
   prepfilesAdditionalCommands:
       - "ln -s /home/ebriand/Projects/__CPH_FF/charmm36m-lambdadyn.ff/"
   ffName: "charmm36m-lambdadyn"
   pdb2gmxAdditionalArguments: " -ignh -ldglu -ldhis -ldasp "
   sodiumName: "SOD"
   chlorideName: "CLA"
   keepawayGroup: "C-alpha"
   distResidueToBuffer: 3.0
   distProteinToBuffer: 2.0
   distBufferTolerance: 0.3
   ionConcentration: 0.150
titration:
   phValues: [-1.0, -0.5, 0.0, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, 8.0, 8.5, 9.0]
   mainRunBarrier: 6.0
   nstlambdaout: 250
localGromacsLaunch:
   gromppThreads: 4
   localGromacsBinary: "/home/ebriand/Projects/gromacs_publication_builds/stable/stable_v1/bin/gmx"
clusterJobLaunch:
   jobPrefix: "LYZ_2"
   clusterLoginNode: "moa1"
   daysForProdRun: 4
   gsubmitCmdLineAddon: " "
   clusterGromacsGMXRC: "/home/ebriand/Projects/gromacs_publication_builds/stable/cluster/stable_v1/bin/GMXRC"
   gsubmitBinary: "/home/ebriand/Projects/git-gromacs-gsubmit-build/bin/g_submit"


```

--------------------------------

### spdlog Build and Installation

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/files/docker/LambdaAnalysis_v3/Dockerfile

Configures, builds, and installs the spdlog library using CMake.

```dockerfile
WORKDIR /universal_build/dependencies/spdlog-1.15.0/
RUN mkdir build
WORKDIR /universal_build/dependencies/spdlog-1.15.0/build/

RUN /universal_build/cmake-3.31.5-linux-x86_64/bin/cmake .. -DBUILD_SHARED_LIBS=OFF -DBUILD_STATIC_LIBS=ON  -DCMAKE_PREFIX_PATH=/universal_build/prefix/ -DCMAKE_INSTALL_PREFIX=/universal_build/prefix/ -DCMAKE_CXX_FLAGS="-march=broadwell -fPIC -static-libgcc -static-libstdc++ "  -DCMAKE_C_FLAGS="-march=broadwell -fPIC -static-libgcc "  -DCMAKE_C_COMPILER=`which gcc-11` -DCMAKE_CXX_COMPILER=`which g++-11` -DCMAKE_BUILD_TYPE=Release

RUN make -j`nproc`
RUN make install
```

--------------------------------

### Lambda Equilibration

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/docs/tutorials/cph-titration

Command to start the lambda equilibration step, allowing protonation states to adapt.

```bash
python titrate_v3.py lambdaequil -r lyzozyme_1.yaml
```

--------------------------------

### Boost Build and Installation

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/files/docker/LambdaAnalysis_v3/Dockerfile

Builds and installs Boost libraries statically, including program_options and filesystem.

```dockerfile
WORKDIR /universal_build/dependencies/boost_1_87_0
RUN mkdir build

RUN ./bootstrap.sh --prefix=/universal_build/prefix/  --with-libraries=program_options,filesystem

RUN ./b2 install --prefix=/universal_build/prefix/ --build-dir=/universal_build/dependencies/boost_1_87_0/staticbuild  --with-program_options --with-filesystem   toolset=gcc-11  link=static cxxflags="-march=broadwell -fPIC -static-libgcc -static-libstdc++  "
```

--------------------------------

### fmt Build and Installation

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/files/docker/LambdaAnalysis_v3/Dockerfile

Configures, builds, and installs the fmt library using CMake.

```dockerfile
WORKDIR /universal_build/dependencies/fmt-11.1.3/
RUN mkdir build
WORKDIR /universal_build/dependencies/fmt-11.1.3/build/

RUN /universal_build/cmake-3.31.5-linux-x86_64/bin/cmake .. -DBUILD_SHARED_LIBS=OFF -DBUILD_STATIC_LIBS=ON  -DCMAKE_PREFIX_PATH=/universal_build/prefix/ -DCMAKE_INSTALL_PREFIX=/universal_build/prefix/ -DCMAKE_CXX_FLAGS="-march=broadwell -fPIC -static-libgcc -static-libstdc++ "  -DCMAKE_C_FLAGS="-march=broadwell -fPIC -static-libgcc "  -DCMAKE_C_COMPILER=`which gcc-11` -DCMAKE_CXX_COMPILER=`which g++-11` -DCMAKE_BUILD_TYPE=Release

RUN make -j`nproc`
RUN make install
```

--------------------------------

### FMM MDP Parameters Example

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/docs/fmm/fmm_parameters

Example of FMM configuration in a GROMACS MDP file.

```mdp
coulombtype                  = FMM      ; Replace "PME" with FMM for coulombtype
fmm-override-multipole-order = 8        ; For most cases: PME-equivalent accuracy
fmm-override-tree-depth      =          ; Depends on the system size, see below

```

--------------------------------

### lmfit Build and Installation

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/files/docker/LambdaAnalysis_v3/Dockerfile

Configures, builds, and installs the lmfit library using CMake.

```dockerfile
WORKDIR /universal_build/dependencies/lmfit/
RUN mkdir build
WORKDIR /universal_build/dependencies/lmfit/build/

RUN /universal_build/cmake-3.31.5-linux-x86_64/bin/cmake .. -DBUILD_SHARED_LIBS=OFF -DBUILD_STATIC_LIBS=ON  -DCMAKE_PREFIX_PATH=/universal_build/prefix/ -DCMAKE_INSTALL_PREFIX=/universal_build/prefix/ -DCMAKE_CXX_FLAGS="-march=broadwell -fPIC -static-libgcc -static-libstdc++ "  -DCMAKE_C_FLAGS="-march=broadwell -fPIC -static-libgcc "  -DCMAKE_C_COMPILER=`which gcc-11` -DCMAKE_CXX_COMPILER=`which g++-11` -DCMAKE_BUILD_TYPE=Release

RUN make -j`nproc`
RUN make install
```

--------------------------------

### OpenBLAS Build and Installation

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/files/docker/LambdaAnalysis_v3/Dockerfile

Builds and installs OpenBLAS with specific compiler flags and target architecture.

```dockerfile
WORKDIR  /universal_build/dependencies/OpenBLAS-0.3.29

RUN make -j`nproc` CC=`which gcc-11` CXX=`which g++-11` FC=`which gfortran-11` TARGET=HASWELL CFLAGS="-march=haswell -fPIC -static-libgcc" CXXFLAGS="-march=haswell -fPIC -static-libgcc -static-libstdc++" FCFLAGS="-march=haswell -fPIC -static-libgcc  -static-libgfortran" PREFIX=/universal_build/prefix

RUN make PREFIX=/universal_build/prefix install
```

--------------------------------

### Verify installation

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/docs/cph-postprocessing/analysis_tool

Run the LambdaAnalysis tool without arguments to check if it's installed correctly.

```bash
./LambdaAnalysis

```

--------------------------------

### Armadillo Build Directory Setup

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/files/docker/LambdaAnalysis_v3/Dockerfile

Sets up the build directory for the Armadillo library.

```dockerfile
WORKDIR /universal_build/dependencies/armadillo-14.2.2/
RUN mkdir build
WORKDIR /universal_build/dependencies/armadillo-14.2.2/build/
```

--------------------------------

### Microstate Titration Command

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/docs/cph-postprocessing/analysis_tool

Example command to run microstate titration analysis.

```bash
./LambdaAnalysis titration \
        --runfile /home/user/titrations/a99_snase_fmm_2.yaml \
        --microstate 1 \
        --output microstate_a99_snase_fmm_2_MI.csv

```

--------------------------------

### Build and Install Vc

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/files/docker/LambdaAnalysis_v3/Dockerfile

Configures and builds the Vc library with specific compiler flags and target architecture.

```dockerfile
WORKDIR /universal_build/dependencies/Vc-1.4.5/
RUN mkdir build
WORKDIR /universal_build/dependencies/Vc-1.4.5/build/

RUN /universal_build/cmake-3.31.5-linux-x86_64/bin/cmake .. -DBUILD_SHARED_LIBS=OFF -DBUILD_STATIC_LIBS=ON  -DCMAKE_PREFIX_PATH=/universal_build/prefix/ -DCMAKE_INSTALL_PREFIX=/universal_build/prefix/ -DCMAKE_CXX_FLAGS="-march=broadwell -fPIC -static-libgcc -static-libstdc++ "  -DCMAKE_C_FLAGS="-march=broadwell -fPIC -static-libgcc "  -DCMAKE_C_COMPILER=`which gcc-11` -DCMAKE_CXX_COMPILER=`which g++-11` -DCMAKE_Fortran_FLAGS=" -march=broadwell -fPIC -static-libgcc  -static-libgfortran "  -DCMAKE_Fortran_COMPILER=/home/ebriand/local/gcc-11/bin/gfortran -DCORE=BROADWELL -DUSE_THREAD=OFF -DCMAKE_SYSTEM_PROCESSOR=broadwell -DBUILD_TESTING=OFF -DTARGET=BROADWELL -DCMAKE_BUILD_TYPE=Release -DTARGET_ARCHITECTURE="broadwell" -DCMAKE_BUILD_TYPE=Release

RUN make -j`nproc`
RUN make install
```

--------------------------------

### Build and Install ensmallen

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/files/docker/LambdaAnalysis_v3/Dockerfile

Configures and builds the ensmallen library with static libraries enabled and OpenMP support.

```dockerfile
WORKDIR /universal_build/dependencies/ensmallen-2.22.1
RUN mkdir build
WORKDIR /universal_build/dependencies/ensmallen-2.22.1/build

RUN /universal_build/cmake-3.31.5-linux-x86_64/bin/cmake .. -DBUILD_SHARED_LIBS=OFF -DBUILD_STATIC_LIBS=ON  -DCMAKE_PREFIX_PATH=/universal_build/prefix/ -DCMAKE_INSTALL_PREFIX=/universal_build/prefix/ -DCMAKE_CXX_FLAGS="-march=broadwell -fPIC -static-libgcc -static-libstdc++ "  -DCMAKE_C_FLAGS="-march=broadwell -fPIC -static-libgcc "  -DCMAKE_C_COMPILER=`which gcc-11` -DCMAKE_CXX_COMPILER=`which g++-11`  -DUSE_OPENMP=ON -DCMAKE_BUILD_TYPE=Release

RUN make -j`nproc`
RUN make install
```

--------------------------------

### SLURM Example Implementation

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/docs/cph/titration_script

A Python function demonstrating a basic SLURM-based implementation using SSH for job submission.

```python
def launchOnCluster(clusterOpts, repDirectory, tprname, jobname, 
                    runname, lambdaoutname, nonLambda=False, continueJob=False):
    # Replace template tokens in SLURM script
    slurm_jobfile = slurm_template.replace('$$$JOBNAME$$$', 
                                         clusterOpts["jobPrefix"] + "_" + jobname)
    slurm_jobfile = slurm_jobfile.replace('$$$GMXSRC_CLUSTER_BUILD$$$', 
                                         clusterOpts["clusterGromacsGMXRC"])
    # ... additional replacements ...

    # Write job script and submit via SSH
    jobfilename = "jobfile_{:05d}.sh".format(random.randrange(50000))
    with open(jobfilename, "w") as f:
        f.write(slurm_jobfile)
    
    command = "ssh {0}@{1} bash -l -c '\"cd {2}; sbatch {3} \"'".format(
        username, clusterOpts["clusterLoginNode"], repDirectory, jobfilename)
    os.system(command)


```

--------------------------------

### File Preparation

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/docs/tutorials/cph-titration

Command to initialize the titration directory structure by copying template files.

```bash
python titrate_v3.py prepfiles -r lyzozyme_1.yaml

```

--------------------------------

### Set the source directory environment variable

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/docs/install_guide

Defines the environment variable CPHSOURCEDIR to point to the source code directory.

```bash
export CPHSOURCEDIR=/directory/with/the/source/ 

```

--------------------------------

### Ion Placement and Energy Minimization (Cluster)

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/docs/tutorials/cph-titration

Command to solvate systems, place ions, and perform energy minimization on a cluster.

```bash
python titrate_v3.py replica_cluster -r lyzozyme_1.yaml

```

--------------------------------

### CMake Installation

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/files/docker/LambdaAnalysis_v3/Dockerfile

Downloads and installs CMake version 3.31.5.

```dockerfile
WORKDIR /universal_build/
RUN wget https://github.com/Kitware/CMake/releases/download/v3.31.5/cmake-3.31.5-linux-x86_64.sh
RUN chmod +x cmake-3.31.5-linux-x86_64.sh
RUN ./cmake-3.31.5-linux-x86_64.sh --skip-license --include-subdir  --prefix=/universal_build/
```

--------------------------------

### Topology Preparation

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/docs/tutorials/cph-titration

Command to generate topology files and initial protein structure using pdb2gmx.

```bash
python titrate_v3.py prereplica -r lyzozyme_1.yaml

```

--------------------------------

### Create Simulation Directory

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/docs/tutorials/cph-titration

Command to create the main simulation directory as specified by the `runDir` parameter in the runfile.

```bash
mkdir lysozyme_1

```

--------------------------------

### Production Runs

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/docs/tutorials/cph-titration

Commands for the production run step, similar to previous steps.

```bash
python titrate_v3.py prod -r lyzozyme_1.yaml
```

```bash
python titrate_v3.py check_prod -r lyzozyme_1.yaml
```

```bash
python titrate_v3.py continue_prod -r lyzozyme_1.yaml
```

```bash
python titrate_v3.py restart_prod -r lyzozyme_1.yaml
```

--------------------------------

### Restart Lambda Equilibration

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/docs/tutorials/cph-titration

Command to restart lambda equilibration jobs if necessary.

```bash
python titrate_v3.py restart_lambdaequil -r lyzozyme_1.yaml
```

--------------------------------

### Example lambda_forms section

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/docs/cph/lambda_cph_topology

An example of a [ lambda_forms ] section containing a site and forms definitions.

```gromacs_topology
[ lambda_forms ]
; Contains autogenerated lambda form for CPH-MD.
; Protonable residue database comment: charmm36m_coupled
; Protonable residue database version:    1

#include "./charmm36m-lambdadyn.ff/cph_lambdasites_bonded.itp"
#include "./charmm36m-lambdadyn.ff/cph_lambdasites_charge.itp"
#include "./charmm36m-lambdadyn.ff/cph_lambdasites_lj.itp"
#include "./charmm36m-lambdadyn.ff/cph_lambdasites_misc.itp"

;                site         form
lambda_site   GLUL_0007
lambda_form   GLUL_0007  GLUL_0007_deprot
lambda_form   GLUL_0007  GLUL_0007_prot_1
lambda_form   GLUL_0007  GLUL_0007_prot_2
;                                  site       molname    molnr  idx_first  idx_last
site_from_continuous_atom_range   GLUL_0007 Protein_chain_A     1    102         118
;                        site         form                     altq_set
alt_q_from_alt_q_set  GLUL_0007  GLUL_0007_deprot           GLUL_deprot_qset
alt_q_from_alt_q_set  GLUL_0007  GLUL_0007_prot_1           GLUL_prot_1_qset
alt_q_from_alt_q_set  GLUL_0007  GLUL_0007_prot_2           GLUL_prot_2_qset

```

--------------------------------

### Solvate the System

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/docs/tutorials/cph-lysozyme-tuto

Standard command to solvate the simulation system.

```bash
gmx solvate -cs spc216.gro -cp box.gro -p topol.top -o solv.gro

```

--------------------------------

### Check Replica Status

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/docs/tutorials/cph-titration

Command to monitor the progress of replica simulations.

```bash
python titrate_v3.py check_replica -r lyzozyme_1.yaml

```

--------------------------------

### Restart Failed Replica Simulations (Local)

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/docs/tutorials/cph-titration

Command to restart failed replica simulations on the local machine.

```bash
# for local launch
python titrate_v3.py restart_replica -r lyzozyme_1.yaml

```

--------------------------------

### Continue Structure Equilibration

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/docs/tutorials/cph-titration

Command to continue structure equilibration from the last checkpoint, useful for long simulations.

```bash
python titrate_v3.py continue_structureequil -r lyzozyme_1.yaml
```

--------------------------------

### Replica Number Example

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/docs/cph/titration_script

Example snippet showing the replicaNumber parameter within the runcontrol section.

```yaml
 runcontrol:
    replicaNumber: 7


```

--------------------------------

### Restart Failed Replica Simulations (Cluster)

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/docs/tutorials/cph-titration

Command to restart failed replica simulations on a cluster.

```bash
# Or alternatively, for cluster launch
python titrate_v3.py restart_replica_cluster -r lyzozyme_1.yaml

```

--------------------------------

### System Package Updates and Installation

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/files/docker/LambdaAnalysis_v3/Dockerfile

Updates package lists, upgrades existing packages, and installs essential build tools and libraries.

```dockerfile
RUN   sed -i 's/# \(.*multiverse$\)/\1/g' /etc/apt/sources.list
RUN   apt-get update
RUN   apt-get -y upgrade
RUN   apt-get install -y build-essential
RUN DEBIAN_FRONTEND=noninteractive apt-get install -y tzdata
RUN   apt-get install -y software-properties-common
RUN   add-apt-repository -y ppa:ubuntu-toolchain-r/test
RUN   apt-get install -y curl git htop man unzip nano wget g++-11 gcc-11 gfortran-11 zlib1g-dev patchelf
```

--------------------------------

### Example output from equil_lambda.dat (comments)

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/docs/tutorials/cph-lysozyme-tuto

The initial lines of the output file contain comments summarizing the simulation settings and internal diagnostics.

```text
; Propagator: ProtTautPropagator
; num residue: 10 | num buffer 10
; dt_ 0.00200   | mass 60.00 
; target temp 300.0
; Using unified output lambda as protonation state: 0
; Charge constraint: SHAKE
; Interpolation Force Manager: ProtTaut Dynamics interpolation manager 
; Interpolation Force Manager: Coupled residue-buffer mode = 1 
; Buffer Manager:  10 buffers total,  10 enabled,   0 directly controlled, 0 disabled
; Collective lambda mass   10.000 max charge    13.0000 min charge    -3.0000
; Coupled buffer formulation: 1
; Collective buffer manager: ProtTaut buffer collective buffer manager 
; Bias: prot-taut double well - PFC? 1
; fixed pH:         7.40 

```

--------------------------------

### Syntax Verification

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/docs/tutorials/cph-titration

Command to check the runfile configuration for syntax errors.

```bash
python titrate_v3.py check_runfile -r lyzozyme_1.yaml

```

--------------------------------

### Dihedral restraints section example

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/docs/cph/lambda_cph_topology

Example of the [dihedral_restraints] section in a topology file, showing parameters for GLUL and ASPL residues.

```gromacs
[ dihedral_restraints ]
; res   i    j    k     l      phi0    deltaPhi   Krestr
GLUL     CG   CD   OE1   HE1    180.0   50.0      30.0
GLUL     CG   CD   OE2   HE2    180.0   50.0      30.0      

; res   i    j    k     l      phi0    deltaPhi   Krestr
ASPL     CB   CG   OD1   HD1    180.0   50.0      30.0
ASPL     CB   CG   OD2   HD2    180.0   50.0      30.0   

```

--------------------------------

### Example `[ constant_ph ]` section

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/docs/cph/lambda_cph_topology

An example configuration for the `[ constant_ph ]` section, including necessary includes and definitions for protonable residue types and their pKa values.

```ini
[ constant_ph ]
; Contains autogenerated protonable residue definition for CPH-MD.
; Protonable residue database comment: charmm36m_coupled
; Protonable residue database version:    1

#include "./charmm36m-lambdadyn.ff/cph_ffcomp.itp"
#include "./charmm36m-lambdadyn.ff/cph_misc.itp"

; -- Common constants --

pka_per_residue_type         GlutamicAcid none 4.0990 4.0990
pka_per_residue_type            Histidine none 6.5300 6.9200
pka_per_residue_type         AsparticAcid none 3.6990 3.6990


; -- Protonable sites --

;                     name     l_mode   restype    site         form1  form2 [form3 ... formN]
protonable_residue   GLUL0007   tl   GlutamicAcid  GLUL_0007  GLUL_0007_deprot      GLUL_0007_prot_1       GLUL_0007_prot_2      
init_lambda_tl   GLUL0007     0.00         0.00 
ffcomp_tl_from_common   GLUL0007     GLUL_QOnly_c 
; pka_override   GLUL0007    none  4.099  4.099  

```

--------------------------------

### Grompp Preprocessing

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/docs/tutorials/cph-lysozyme-tuto

Command to preprocess the simulation input files for the production run.

```bash
gmx grompp -f production_lambda.mdp -c equil_structure.gro -r equil_structure.gro \
            -o production.tpr -p topol.top -t equil_structure.cpt

```

--------------------------------

### Generate ions with genion

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/docs/tutorials/cph-lysozyme-tuto

Generates ions using genion with specific constant pH options for buffer site placement.

```bash
gmx genion -s genion.tpr -o solvions.gro \
           -p topol.top -pname SOD -nname CLA \
           -conc 0.150 -neutral \
           -cphcoupled -rminprotld 2.0 -rminld 3.0 -rtolld 0.3

```

--------------------------------

### Example .dat trajectory output

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/docs/cph/raw_dat_output_format

Shows an example of the .dat trajectory file, including comment lines and a data line, illustrating the space-separated fields.

```text
; [ time ] [ RorB ] [ site ] [ l_p ] [ l_t ] [ v_p ] [ v_t ] [ f_p ] [ f_t ] [ dhdl_p ] [ dhdl_t ] [ ffcomp_p ] [ ffcomp_t ] [ bias_p ] [ bias_t ] [ constr_p ] [ constr_buff ] [ f_buff ] [ therm ] [ inhib ] 
; Restarting from checkpoint
; Starting internal state is:
;     residue [   0]  lambda_p =         1.0757195950   velocity =         -0.0104046911  last_force =      -205.1779327393
;                     lambda_t =         0.7902489305   velocity =          0.0634180531 last_force =         9.1901779175
; Reading buffer checkpoint:
;      collective buffer lambda         0.0000000000 (v:         0.0000000000  F_(t-1)         0.0000000000)
      0.000  r   0 1.075687 0.790344 -0.012844 0.047467 -205.095459 9.176412 107.917526 57.379688 212.144714 56.451721 -100.868263 8.248445 0.000000 0.000000 0.000000   0   0
      0.000  b   0 -0.075687 0.000000 0.000000 0.000000 0.000000 0.000000 0.000000 0.000000 0.000000 0.000000 823710461516290818310144.000000 0.000000 0.000000 0.000000 0.000000   0   0

```

--------------------------------

### Generate tpr file for energy minimization

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/docs/tutorials/cph-lysozyme-tuto

Generates a tpr file for energy minimization using the em.mdp settings file, the solvions.gro configuration, and the topol.top topology.

```bash
gmx grompp -f em.mdp -c solvions.gro  -o em.tpr -p topol.top 

```

--------------------------------

### Build and Install oneTBB

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/files/docker/LambdaAnalysis_v3/Dockerfile

Configures and builds the oneTBB library with shared libraries enabled.

```dockerfile
WORKDIR /universal_build/dependencies/oneTBB-2022.0.0
RUN mkdir build
WORKDIR /universal_build/dependencies/oneTBB-2022.0.0/build


RUN /universal_build/cmake-3.31.5-linux-x86_64/bin/cmake .. -DBUILD_SHARED_LIBS=ON -DBUILD_STATIC_LIBS=OFF  -DCMAKE_PREFIX_PATH=/universal_build/prefix/ -DCMAKE_INSTALL_PREFIX=/universal_build/prefix/ -DCMAKE_CXX_FLAGS="-march=broadwell -fPIC -static-libgcc -static-libstdc++ "  -DCMAKE_C_FLAGS="-march=broadwell -fPIC -static-libgcc "  -DCMAKE_C_COMPILER=`which gcc-11` -DCMAKE_CXX_COMPILER=`which g++-11` -DTBB_TEST=ON -DCMAKE_BUILD_TYPE=Release

RUN make -j`nproc`
RUN make install
```

--------------------------------

### Run energy minimization

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/docs/tutorials/cph-lysozyme-tuto

Executes the energy minimization process using the generated em.tpr file.

```bash
gmx mdrun -deffnm em -v

```

--------------------------------

### Base Ubuntu Image and User Setup

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/files/docker/LambdaAnalysis_v3/Dockerfile

Sets the base image to Ubuntu 20.04, switches to root user, and creates a working directory.

```dockerfile
FROM ubuntu:20.04 as base

USER 0

WORKDIR /

RUN mkdir /universal_build

WORKDIR /universal_build
```

--------------------------------

### Build and Install GROMACS

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/files/docker/LambdaAnalysis_v3/Dockerfile

Configures and builds GROMACS with static libraries and specific compiler flags.

```dockerfile
RUN LD_LIBRARY_PATH=/universal_build/prefix/lib:/universal_build/prefix/lib64:/usr/lib/gcc/x86_64-linux-gnu/11/:/usr/lib/x86_64-linux-gnu/ /universal_build/cmake-3.31.5-linux-x86_64/bin/cmake .. -DBUILD_SHARED_LIBS=OFF -DBUILD_STATIC_LIBS=ON  -DCMAKE_PREFIX_PATH=/universal_build/prefix/ -DCMAKE_INSTALL_PREFIX=/universal_build/prefix/ -DCMAKE_CXX_FLAGS="-march=broadwell -fPIC -pthread -ldl -lgfortran -static-libgcc -static-libstdc++ "  -DCMAKE_C_FLAGS="-march=broadwell -pthread -ldl -lgfortran -fPIC -static-libgcc "  -DCMAKE_C_COMPILER=`which gcc-11` -DCMAKE_CXX_COMPILER=`which g++-11` -DSTATIC_LIB=ON -DOPENBLAS_PROVIDES_LAPACK=ON -DALLOW_FLEXIBLAS_LINUX=OFF -DARMA_LIBS="/universal_build/prefix/lib/libopenblas.a;/usr/lib/gcc/x86_64-linux-gnu/11/libgfortran.a;/usr/lib/gcc/x86_64-linux-gnu/11/libquadmath.a" -DCMAKE_BUILD_TYPE=Release

RUN LD_LIBRARY_PATH=/universal_build/prefix/lib:/universal_build/prefix/lib64:/usr/lib/gcc/x86_64-linux-gnu/11/:/usr/lib/x86_64-linux-gnu/ make -j`nproc`

RUN make install
```

--------------------------------

### Check glibc version

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/docs/cph-postprocessing/analysis_tool

Command to check the installed glibc version on the system.

```bash
ldd --version

```

--------------------------------

### Check Lambda Equilibration Status

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/docs/tutorials/cph-titration

Command to check the completion status of replicas during lambda equilibration.

```bash
python titrate_v3.py check_lambdaequil -r lyzozyme_1.yaml
```

--------------------------------

### Titration plot function

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/files/Titration_lyzozyme_example.ipynb

Defines a function to create a titration plot for a given site.

```python
def make_titration_plot(ax, site):


```

--------------------------------

### Calculate FractionTransition

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/files/Titration_lyzozyme_example.ipynb

This code snippet calculates the 'FractionTransition' column by dividing 'frameProtMiddleForDynBias' by 'frameCount'.

```python
df["FractionTransition"] = df["frameProtMiddleForDynBias"] / (df["frameCount"])
```

--------------------------------

### Directory structure for undoing changes

Source: https://grubmueller.pages.mpcdf.de/docs-gromacs-fmm-constantph/docs/tutorials/cph-lysozyme-tuto

Executing each step in a separate directory allows for easier undoing of changes by deleting and copying directories.

```bash
mkdir topology_creation; cd topology_creation
gmx pdb2gmx ...
cd ..
cp -r topology_creation solvation
cd solvation
gmx solvate ...
...

```
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