Computation of Protein-Ligand Binding Free Energies with a Quantum Mechanics-Based Mining Minima Algorithm.

ABSTRACT: A new method, protein-ligand QM-VM2 (PLQM-VM2), to calculate protein-ligand binding free energies by combining mining minima, a statistical mechanics end-point-based approach, with quantum mechanical potentials is presented. PLQM-VM2 is described in terms of a highly flexible workflow that is initiated from a Protein Data Bank (PDB) file and a chemical structure data file (SD file) containing two-dimensional (2D) or three-dimensional (3D) ligand series coordinates. The workflow utilizes the previously developed molecular mechanics (MM) implementation of the second-generation mining minima method, MM-VM2, to provide ensembles of protein, free ligand, and protein-ligand conformers, which are postprocessed at chosen levels of QM theory, via the quantum chemistry software package GAMESS, to co

SUBMITTER: Schlinsog M 

PROVIDER: S-EPMC12020368 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature