Ligand Gaussian Accelerated Molecular Dynamics 2 (LiGaMD2): Improved Calculations of Ligand Binding Thermodynamics and Kinetics with Closed Protein Pocket.

ABSTRACT: Ligand binding thermodynamics and kinetics are critical parameters for drug design. However, it has proven challenging to efficiently predict ligand binding thermodynamics and kinetics from molecular simulations due to limited simulation timescales. Protein dynamics, especially in the ligand binding pocket, often plays an important role in ligand binding. Based on our previously developed Ligand Gaussian accelerated molecular dynamics (LiGaMD), here we present LiGaMD2 in which a selective boost potential was applied to both the ligand and protein residues in the binding pocket to improve sampling of ligand binding and dissociation. To validate the performance of LiGaMD2, the T4 lysozyme (T4L) mutants with open and closed pockets bound by different ligands were chosen as model systems. LiGa

SUBMITTER: Wang J 

PROVIDER: S-EPMC10316156 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature