drug-protein-ligand-md

drug-protein-ligand-md

Goal

To run a complete protein-ligand molecular dynamics simulation using OpenMM, starting from a system bundle produced by drug-complex-system-builder. The workflow includes:

1. Energy minimization
2. NVT equilibration with positional restraints on heavy atoms
3. NPT equilibration with restraints gradually released
4. NPT production run

The output is a DCD trajectory + final state checkpoint suitable for drug-trajectory-analysis.

Instructions

1. Prepare inputs

Required from drug-complex-system-builder:

• system.xml: serialized OpenMM System
• complex_solvated.pdb: solvated complex PDB (used as topology reference)

2. Run the simulation

# Env: drugmd-agent
python .agents/skills/drug-protein-ligand-md/scripts/run_md.py \
  --system_xml md/system/system.xml \
  --input_pdb md/system/complex_solvated.pdb \
  --temperature 300 \
  --pressure 1.0 \
  --timestep 4.0 \
  --minimize_steps 5000 \
  --equil_nvt_steps 25000 \
  --equil_npt_steps 50000 \
  --production_steps 2500000 \
  --restraint_k 50.0 \
  --reporting_interval 5000 \
  --checkpoint_interval 25000 \
  --output_dir md/run/

Key parameters:

• --temperature: simulation temperature in Kelvin (default: 300).
• --pressure: target pressure in atm (default: 1.0).
• --timestep: integration timestep in fs (default: 4.0). 4 fs is safe with hydrogen mass repartitioning (HMR) from the system builder; use 2 fs without HMR.
• --minimize_steps: max minimization steps (default: 5000). Set to 0 to skip.
• --equil_nvt_steps: NVT equilibration steps with restraints on protein/ligand heavy atoms (default: 25000 = 100 ps at 4 fs).
• --equil_npt_steps: NPT equilibration steps with restraints released (default: 50000 = 200 ps).
• --production_steps: production NPT steps (default: 2500000 = 10 ns at 4 fs).
• --restraint_k: restraint force constant for equilibration in kJ/mol/nm^2 (default: 50.0).
• --reporting_interval: write trajectory frame every N steps (default: 5000 = 20 ps).
• --checkpoint_interval: write checkpoint every N steps (default: 25000).