Toward Automated Free Energy Calculation with Accelerated Enveloping Distribution Sampling (A-EDS).

ABSTRACT: Free-energy perturbation (FEP) methods are commonly used in drug design to calculate relative binding free energies of different ligands to a common host protein. Alchemical ligand transformations are usually performed in multiple steps which need to be chosen carefully to ensure sufficient phase-space overlap between neighboring states. With one-step or single-step FEP techniques, a single reference state is designed that samples phase-space not only representative of a full transformation but also ideally resembles multiple ligand end states and hence allows for efficient multistate perturbations. Enveloping distribution sampling (EDS) is one example for such a method in which the reference state is created by a mathematical combination of the different ligand end states based on solid s

SUBMITTER: Perthold JW 

PROVIDER: S-EPMC7686955 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature