Input Preparation

Before running MD, ensure the system is correctly prepared to avoid failures during topology generation or simulation.

Hydrogen Handling and Protonation

StreaMD re-adds hydrogens by default using gmx pdb2gmx -ignh. This ignores original hydrogens and recreates them based on residue names.

CAUTION: Rename residues to match correct protonation states (CYS->CYX, HIS->HID/HIE/HIP) before running. If you prefer to keep existing hydrogens, pass --noignh, but you must resolve any atom name recognition issues yourself or provide prepared protein.gro, topol.top, and posre.itp.

Target Preparation

  • Fill missing residues and loops.

  • Optional: remove explicit water and cofactors from crystal structures unless they must be retained.

  • Remove co-crystallized ligands.

  • Add hydrogens according to protonation states; rename histidines to HID/HIE/HIP as appropriate.

  • Co-crystallized ligands can be downloaded from the PDB as .sdf and prepared separately.

  • Chimera commands for histidine renaming:

    setattr r type HID :HIS@HD1,DD1,TD1,HND
setattr r type HIP :HID@HE2,DE2,TE2
setattr r type HIE :HIS@HE2

  • Optional tooling: Chimera (Modeller loop/refinement, Dock Prep), pdbfixer or pdb4amber.

Prepared examples and scripts: https://github.com/ci-lab-cz/docking-files

Ligand Preparation (Optional)

  • Ensure ligand/cofactor coordinates are aligned to the protein if running multiple ligands.

  • Ligands/cofactors must be provided as .mol or .sdf files with correct 3D coordinates, hydrogens, protonation state, stereochemistry, and desired tautomer; StreaMD does not fix these automatically.

Docking Procedure (Optional)

If ligand poses are needed, perform docking before MD:

  • Use EasyDock for automated docking: https://github.com/ci-lab-cz/easydock

  • EasyDock can handle protonation and stereoisomers and produces docking poses in .sdf, matching the required input format.

Ready to run? Proceed to Running Molecular Dynamics for command examples and continuation/extension workflows.