ProtoCaller

ProtoCaller automates relative protein-ligand binding free energy calculations within the GROMACS molecular dynamics environment for biomolecular simulation studies.

Key Features:

• Automation of RBFE calculations: Automates relative protein-ligand binding free energy workflows targeting GROMACS molecular dynamics simulations.
• Integrations with preparation tools: Interfaces with PDB2PQR, Modeller, and AmberTools for protein and ligand preparation and parametrization.
• Force field support: Supports AMBER force fields and incorporates additional cofactor parameters.
• Ligand charge derivation: Employs the AM1-BCC method for ligand partial charge assignment.
• PDB parsing: Provides a comprehensive PDB parser for robust structure data handling and manipulation.
• Enhanced MCS algorithm: Implements an enhanced maximum common substructure algorithm to improve ligand-ligand mapping accuracy.
• GROMACS wrapper: Includes a lightweight wrapper to launch and manage multiple GROMACS molecular dynamics simulations.

Scientific Applications:

• Binding free energy calculations: Enables relative binding free energy estimation for protein-ligand systems.
• Protein and ligand parametrization: Facilitates preparation and parameter assignment for proteins, ligands, and cofactors using AMBER force fields and AM1-BCC charges.
• Ligand mapping and perturbation studies: Supports ligand-ligand mapping for studies involving multiple ligands or complex binding scenarios.
• Biomolecular simulation workflows: Integrates preparation, parametrization, mapping, and MD execution for biomolecular simulation research.

Methodology:

Uses PDB2PQR, Modeller, and AmberTools for preparation, AM1-BCC for ligand charges, AMBER force fields with additional cofactor parameters, an enhanced maximum common substructure algorithm for ligand mapping, and a GROMACS wrapper to run molecular dynamics for relative binding free energy calculations.