OpenFF Protein-Ligand MD

Solvate a protein-ligand complex, parameterize it with OpenFF Sage + ff14SB, run independent OpenMM replicas in parallel and report protein and ligand RMSD.

by Temple Compute

Run OpenFF Protein-Ligand MD on Horus

W-39 · OpenFF Protein-Ligand MD

Solvate a protein-ligand complex, parameterize it with OpenFF Sage + ff14SB, run independent OpenMM replicas in parallel and report protein and ligand RMSD.

Domain: OMSF

Overview

Solvates the HIF-2α PAS-B domain (PDB 5TBM) with the inhibitor PT2385, parameterizes the protein with ff14SB and the ligand, water and ions with OpenFF Sage 2.3.0 (through Interchange), runs independent OpenMM replicas and reports protein and ligand RMSD. It is a port of the Open Force Field Toolkit Showcase (openff-toolkit 0.19.0). The workflow has 4 tasks.

Pipeline

build_system  PDBFixer + OpenFF Topology        --> system/topology.json
parameterize  Interchange                       --> replicas/<i>/{system.xml,complex.pdb,seed}
simulate      horus_map, 1 clone per replica    --> trajectories/<i>/ (OpenMM minimize + Langevin MD)
analyze       mdtraj RMSD                       --> results/{rmsd.csv,report.html,final_frame.pdb}

Inputs / Outputs

receptor: prepared PDB (protonated, capped, no missing atoms, no ligand). Default examples/5tbm_prepared.pdb.
ligand: SDF with explicit hydrogens, posed in the pocket; the residue is named UNK. Default examples/PT2385.sdf.
results/rmsd.csv: replica, frame, time_ps, protein_ca_rmsd_A, ligand_rmsd_A. Ligand RMSD is measured after aligning on protein Cα atoms.
results/report.html: per-replica summary and a Mol* view of the final frame, titled with system_label. results/final_frame.pdb: last frame of replica 0.
trajectories/<i>/: trajectory.dcd, log.csv, complex.pdb, seed.

Parameters

| id | Default | Meaning | |---|---|---| | receptor / ligand | 5TBM / PT2385 examples | Inputs above | | system_label | PT2385 / HIF-2α (5TBM) | System name in the report title | | n_replicas | 3 | Independent replicas (1-100) | | n_steps | 500000 | MD steps per replica (1 ns at 2 fs; 1000-50,000,000) | | padding_nm | 1.0 | Solvent padding around the protein (0.5-5) | | ionic_strength_molar | 0.15 | NaCl ionic strength (0-2) | | temperature_k | 300 | Thermostat temperature (250-400) | | timestep_fs | 2 | Integrator timestep, H bonds constrained (0.5-4) | | report_interval_steps | 5000 | Steps between DCD frames and log.csv rows; must not exceed n_steps (100-1,000,000) |

Seeds are 2026 + replica index.

References

OpenFF Toolkit
OpenFF Interchange
OpenMM
PDBFixer
MDTraj
OMSF workflow directory
OpenFF Toolkit docs
OpenFF Interchange docs