Generalizing the Discrete Gibbs Sampler-Based λ-Dynamics Approach for Multisite Sampling of Many Ligands.

ABSTRACT: In this work, the discrete λ variant of the Gibbs sampler-based λ-dynamics (d-GSλD) method is developed to enable multiple functional group perturbations to be investigated at one or more sites of substitution off a common ligand core. The theoretical framework and special considerations for constructing discrete λ states for multisite d-GSλD are presented. The precision and accuracy of the d-GSλD method is evaluated with three test cases of increasing complexity. Specifically, methyl → methyl symmetric perturbations in water, 1,4-benzene hydration free energies and protein-ligand binding affinities for an example HIV-1 reverse transcriptase inhibitor series are computed with d-GSλD. Complementary MSλD calculations were also performed to compare with d-GS

SUBMITTER: Vilseck JZ 

PROVIDER: S-EPMC8627277 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature