Evaluating the FEP+ protocol for predicting binding affinity of congeneric ligands towards various soluble proteins.

ABSTRACT: Generating libraries of congeneric series of compounds and development of structure-activity relationships (SAR) is a common practice among medicinal chemists. While various computational methods are available to guide scaffold optimization, their reliability in prediction can vary. Ligand free energy perturbation (FEP+) is a rigorous computational program that computes the relative binding free energies between two congeneric ligands against a target, thereby identifying the ligand with greater binding affinity. In this study, we evaluated the FEP+ method to predict the relative binding affinity of two ligands from a congeneric series towards the target proteins. A total of 34 ligand transformations were performed, spanning across 21 soluble proteins. Relative binding free energies were c

SUBMITTER: Sampangin Venkatesh SK 

PROVIDER: S-EPMC12679534 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature