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GROMACS Peptide Simulation Tutorial

This tutorial will walk you through simulating peptide systems in GROMACS, including custom D-amino acids.

Required Files

Download all necessary files from this Google Drive folder: Simulation Files

If you’re new to GROMACS, consider starting with this basic tutorial on lysozyme.

Custom D-Amino Acids

To simulate D-amino acids:

  • Include a residuetype.dat file to introduce your new residue into the force field.
  • This file must be in the same directory as your system-building scripts.
  • Use a 3- or 4-letter code (e.g., DTYR, DPHE) that matches your Avogadro output.

Example:

residuetype.dat screenshot

Step 1: Build the Amino Acid (Avogadro)

Follow this Avogadro tutorial to build and save your peptide (e.g., dkyfilinvert.pdb).

Step 2: Load GROMACS on Rivanna

Open a terminal on Rivanna and load the required modules:

module load gcc/11.4.0 openmpi/4.1.4 gromacs/2023.2

Step 3: Convert PDB to GROMACS Format

Convert your .pdb file to .gro using:

gmx_mpi pdb2gmx -f dkyfilinvert.pdb -o dkyfil.gro

Choose these options when prompted:

  • Force field: 1 (CHARMM)
  • Water model: 1 (TIP3P)
  • Terminal capping: 2 (CT2 to amidate Leu C-terminus)

Step 4: Create a 3D Peptide Grid

Use genconf to create a randomized peptide box (e.g., 4x4x4 = 64 peptides):

gmx_mpi genconf -f dkyfil.gro -nbox 4 4 4 -rot yes -dist 1.6243 2.5864 1.8081 -o dKYFIL_64_box.gro
  • -rot yes: Randomly rotates each peptide.
  • -dist: Distance (in nm) between peptides in x, y, z directions.

Step 5: Solvate the System

Add water and generate a topology file:

gmx_mpi solvate -cp KYFIL_64_peptides.gro -o KYFIL_64_peptides_solvate.gro -p topol.top

Step 6: Prepare for Ion Addition

Generate the machine-readable .tpr file:

gmx_mpi grompp -f ions.mdp -c KYFIL_64_peptides_solvate.gro -p topol.top -o ions.tpr

Step 7: Add Ions (Neutralize & Set 150 mM Salt)

gmx_mpi genion -s ions.tpr -o dkyfil_64_peptides_solvate_ions.gro -p topol.top -pname NA -nname CL -neutral -conc 0.15

When prompted, select group 13 (SOL) to replace water with ions.

Step 8: Energy Minimization

Create the energy minimization input:

gmx grompp -f minim.mdp -c KYFIL_64_peptides_solvate_ions.gro -p topol.top -o em.tpr

Then run the following SLURM script to perform energy minimization:

#!/bin/bash
#SBATCH --nodes=7
#SBATCH --ntasks-per-node=36
#SBATCH --mail-user=[computingID]@virginia.edu
#SBATCH --mail-type=END,FAIL,TIME_LIMIT
#SBATCH --time=3-00:00:00
#SBATCH --partition=parallel
#SBATCH -A [allocation]
#SBATCH -o minimize.out

module purge
module load gcc/11.4.0 openmpi/4.1.4 gromacs/2023.2
gmx mdrun -v -deffnm em

Step 9: Molecular Dynamics (MD) Run Prep

Generate the MD .tpr file:

gmx grompp -f md.mdp -c em.gro -r em.gro -p topol.top -o md.tpr

Then submit this SLURM job script to run the full simulation:

#!/bin/bash
#SBATCH --nodes=7
#SBATCH --ntasks-per-node=36
#SBATCH --mail-user=[computingID]@virginia.edu
#SBATCH --mail-type=END,FAIL,TIME_LIMIT
#SBATCH --time=3-00:00:00
#SBATCH --partition=parallel
#SBATCH -A [allocation]
#SBATCH -o dynamicrun.out

module purge
module load gcc/11.4.0 openmpi/4.1.4 gromacs/2023.2
gmx mdrun -v -deffnm md

You're Done!

Your simulation is now running. When complete, you'll have .gro, .xtc, and .edr files ready for analysis.