Fast free energy estimates from λ-dynamics with bias-updated Gibbs sampling.

ABSTRACT: Relative binding free energy calculations have become an integral computational tool for lead optimization in structure-based drug design. Classical alchemical methods, including free energy perturbation or thermodynamic integration, compute relative free energy differences by transforming one molecule into another. However, these methods have high operational costs due to the need to perform many pairwise perturbations independently. To reduce costs and accelerate molecular design workflows, we present a method called λ-dynamics with bias-updated Gibbs sampling. This method uses dynamic biases to continuously sample between multiple ligand analogues collectively within a single simulation. We show that many relative binding free energies can be determined quickly with this approach withou

SUBMITTER: Robo MT 

PROVIDER: S-EPMC10740020 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature