Proposed new modular BAC design

Initial development priorities in bold

System Preparation (Builder)

Drug Parameterization

• Initially target GAFF/AM1-BCC with ANTECHAMBER
• Start from mol2, pdb or SMILES
• Select protonation state
• Need to create hybrid topologies (TIES)

Model completion

• Model missing loops
• Apply biological unit (BIOMT)
• Create from new PDB format XML/mmCIF
• Parameterize or replace non standard residues

Simulation system preparation

• Apply user specified mutations to proteins
  • Insertions and deletions
  • Specify by target sequence (or relative to reference)
• Homology modelling
• Select residue protonation states
• Incorporate disulphides
• Ions
  • Load parameters if necessary
  • Option to build binding site using explicit bonds?
• Solvate
  • Counter ions
  • Select pH [New] ?
  • Select geometry [New] ?
• Prepare topology
  • AMBER
  • CHARMM
  • GROMOS
  • OPLS
  • Joint/multiple topologies for TI

Generate simulation configuration/run files

Vanilla MD

• NAMD
• OpenMM
• CHARMM
• AMBER
• GROMACS

Alchemical

• NAMD
• OpenMM
• CHARMM
• AMBER
• GROMACS

MIST

• GROMACS

Drug docking

Metadata

• System specification (forcefield, sequence etc.)
• Extract version of simulation code from logs

BAC Analyse

• MMPBSA
• Normal mode
• TI
• ABFE
• Structural analyses
  • User specified scripts?
  • Standard analses
• Automated equilibration analysis example code
• MSM