Binding free energy of protein/ligand complexes calculated using dissociation Parallel Cascade Selection Molecular Dynamics and Markov state model.

ABSTRACT: We recently proposed a computational procedure to simulate the dissociation of protein/ligand complexes using the dissociation Parallel Cascade Selection Molecular Dynamics simulation (dPaCS-MD) method and to analyze the generated trajectories using the Markov state model (MSM). This procedure, called dPaCS-MD/MSM, enables calculation of the dissociation free energy profile and the standard binding free energy. To examine whether this method can reproduce experimentally determined binding free energies for a variety of systems, we used it to investigate the dissociation of three protein/ligand complexes: trypsin/benzamine, FKBP/FK506, and adenosine A_{2 A} receptor/T4E. First, dPaCS-MD generated multiple dissociation pathways within a reasonable computational time for al

SUBMITTER: Hata H 

PROVIDER: S-EPMC8694779 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature