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Simple Protein-Ligand Example

Quick Start

prism protein.pdb ligand.mol2 -o t4l_benzene
cd t4l_benzene/GMX_PROLIG_MD && bash localrun.sh

A complete, minimal example demonstrating the PRISM workflow from input files to a production-ready MD system.

Overview

This example shows how to:

  • Build a protein-ligand system with default settings
  • Generate all necessary GROMACS files
  • Run molecular dynamics simulations

Complexity: Beginner Time: ~10 minutes (system building) + simulation time System: T4 Lysozyme L99A/M102Q + Benzene (PDB: 5JWT)

Download Example Files

Pre-processed input files are provided. The protein structure has been cleaned (solvent/ions removed, hydrogens added) and the ligand has been prepared in MOL2 format with correct atom types.

protein.pdb (112 KB)

ligand.mol2 (1 KB)

Or download via command line:

mkdir simple_example && cd simple_example

# Download from the PRISM Tutorial repository
wget https://raw.githubusercontent.com/AIB100/PRISM-Tutorial/main/docs/assets/examples/md/protein.pdb
wget https://raw.githubusercontent.com/AIB100/PRISM-Tutorial/main/docs/assets/examples/md/ligand.mol2

Your directory should contain:

simple_example/
├── protein.pdb    # T4 Lysozyme L99A/M102Q (164 residues, 1309 atoms)
└── ligand.mol2    # Benzene (12 atoms: 6C + 6H)

Step 1: Build the System

Command Line

prism protein.pdb ligand.mol2 -o t4l_benzene

Python API

import prism as pm

system = pm.system("protein.pdb", "ligand.mol2", output_dir="t4l_benzene")
system.build()

PRISM will automatically:

  1. Generate ligand force field parameters (GAFF by default)
  2. Prepare the protein topology (AMBER99SB-ILDN by default)
  3. Combine protein and ligand into a complex
  4. Solvate in a TIP3P water box
  5. Add Na+/Cl- ions for charge neutralization (0.15 M)
  6. Generate MDP files for all simulation stages
  7. Create a ready-to-run simulation script

Output Structure

t4l_benzene/
├── LIG.amb2gmx/              # Ligand force field files
│   ├── LIG.gro               # Ligand coordinates
│   ├── LIG.itp               # Ligand topology
│   └── ...
├── GMX_PROLIG_MD/            # Simulation directory
│   ├── solv_ions.gro         # Solvated system
│   ├── topol.top             # System topology
│   └── localrun.sh           # Run script
└── mdps/                     # MD parameter files
    ├── em.mdp                # Energy minimization
    ├── nvt.mdp               # NVT equilibration
    ├── npt.mdp               # NPT equilibration
    └── md.mdp                # Production MD

Step 2: Run the Simulation

cd t4l_benzene/GMX_PROLIG_MD
bash localrun.sh

The script runs four stages sequentially:

Stage Purpose Typical Time (GPU)
Energy Minimization Remove bad contacts ~2 minutes
NVT Equilibration Heat to 300 K ~10 minutes
NPT Equilibration Equilibrate pressure ~10 minutes
Production MD Data collection 2-4 hours (for 100 ns)

Monitor Progress

# Check which stage is running
ls -lh em/ nvt/ npt/ prod/

# Watch the production MD log
tail -f prod/md.log

Step 3: Check Results

After simulation completes, verify the output:

# Check production trajectory exists
ls -lh prod/md.xtc

# Quick energy check
gmx energy -f prod/md.edr -o energy.xvg

Expected System Statistics

Property Expected Value
Total atoms ~25,000-35,000
Protein atoms 1,309
Ligand atoms 12
Water molecules ~8,000-11,000
Na+/Cl- ions ~20-40

Customization

Change Force Field

# Use OpenFF for ligand, AMBER14SB for protein
prism protein.pdb ligand.mol2 -o t4l_benzene \
    --ligand-forcefield openff --forcefield amber14sb

Adjust Simulation Length

Edit mdps/md.mdp before running, or use configuration:

prism protein.pdb ligand.mol2 -o t4l_benzene --production-time 500

Change Water Model

prism protein.pdb ligand.mol2 -o t4l_benzene --water tip4p

Troubleshooting

"GROMACS command not found": Source the GROMACS environment first: 

source /path/to/gromacs/bin/GMXRC

"Cannot generate GAFF parameters": Install AmberTools and ACPYPE: 

conda install -c conda-forge ambertools
pip install acpype

"Ligand parameterization failed": Try OpenFF as an alternative: 

prism protein.pdb ligand.mol2 -o t4l_benzene --ligand-forcefield openff

What's Next