Leveraging a Separation of States Method for Relative Binding Free Energy Calculations in Systems with Trapped Waters.

ABSTRACT: Methods for calculating the relative binding free energy (RBFE) between ligands to a target protein are gaining importance in the structure-based drug discovery domain, especially as methodological advances and automation improve accuracy and ease of use. In an RBFE calculation, the difference between the binding affinities of two ligands to a protein is calculated by transforming one ligand into another, in the protein-ligand complex, and in solvent. Alchemical binding free energy calculations are often used for such ligand transformations. Such calculations are not without challenges, however; for example, it can be challenging to handle interfacial waters when these play a crucial role in mediating protein-ligand binding. In some cases, the exchange of the interfacial waters with solven

SUBMITTER: Wagle S 

PROVIDER: S-EPMC11672664 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature