Comparison of Receptor-Ligand Restraint Schemes for Alchemical Absolute Binding Free Energy Calculations.

ABSTRACT: Alchemical absolute binding free energy calculations are of increasing interest in drug discovery. These calculations require restraints between the receptor and ligand to restrict their relative positions and, optionally, orientations. Boresch restraints are commonly used, but they must be carefully selected in order to sufficiently restrain the ligand and to avoid inherent instabilities. Applying multiple distance restraints between anchor points in the receptor and ligand provides an alternative framework without inherent instabilities which may provide convergence benefits by more strongly restricting the relative movements of the receptor and ligand. However, there is no simple method to calculate the free energy of releasing these restraints due to the coupling of the internal and ex

SUBMITTER: Clark F 

PROVIDER: S-EPMC10308817 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature