molecular-dynamics-guide

Molecular Dynamics Guide

A skill for setting up, running, and analyzing molecular dynamics (MD) simulations. Covers force field selection, system preparation, simulation protocols, trajectory analysis, and free energy calculations using GROMACS, OpenMM, and MDAnalysis.

System Preparation

Building a Simulation System

The standard workflow for preparing an MD simulation:

1. Obtain structure (PDB, homology model, or docking pose)
2. Clean structure (add missing atoms, fix protonation states)
3. Assign force field parameters
4. Solvate in explicit water box
5. Add counterions to neutralize charge
6. Energy minimize
7. Equilibrate (NVT then NPT)
8. Production run

GROMACS System Setup

# 1. Generate topology from PDB
gmx pdb2gmx -f protein.pdb -o processed.gro -water tip3p -ff amber99sb-ildn

# 2. Define simulation box (dodecahedron, 1.0 nm buffer)
gmx editconf -f processed.gro -o boxed.gro -c -d 1.0 -bt dodecahedron

# 3. Solvate
gmx solvate -cp boxed.gro -cs spc216.gro -o solvated.gro -p topol.top

# 4. Add ions to neutralize and set ionic strength (0.15 M NaCl)
gmx grompp -f ions.mdp -c solvated.gro -p topol.top -o ions.tpr
gmx genion -s ions.tpr -o ionized.gro -p topol.top -pname NA -nname CL -neutral -conc 0.15

# 5. Energy minimization
gmx grompp -f minim.mdp -c ionized.gro -p topol.top -o em.tpr
gmx mdrun -deffnm em

# 6. NVT equilibration (100 ps, 300 K)
gmx grompp -f nvt.mdp -c em.gro -r em.gro -p topol.top -o nvt.tpr
gmx mdrun -deffnm nvt

# 7. NPT equilibration (100 ps, 300 K, 1 bar)
gmx grompp -f npt.mdp -c nvt.gro -r nvt.gro -t nvt.cpt -p topol.top -o npt.tpr
gmx mdrun -deffnm npt

# 8. Production MD (100 ns)
gmx grompp -f md.mdp -c npt.gro -t npt.cpt -p topol.top -o md.tpr
gmx mdrun -deffnm md

Force Field Selection

Common Force Fields

Force Field	Strengths	Typical Use
AMBER ff14SB	Protein structure, dynamics	Protein simulations
AMBER ff19SB	Improved backbone dihedrals	Latest protein simulations
CHARMM36m	Proteins, lipids, carbohydrates	Membrane systems
OPLS-AA/M	Small molecules, organic liquids	Drug-like molecules
GAFF2	General small molecules	Ligand parameterization
CGenFF	CHARMM-compatible small molecules	Ligands in CHARMM systems