IMERGE-FEP: Improving Relative Free Energy Calculation Convergence with Chemical Intermediates.

ABSTRACT: Alchemical free energy calculations are becoming an increasingly prevalent tool in drug discovery efforts. Over the past decade, significant progress has been made in automating various aspects of this technique. However, one aspect hampering wider application is the construction of perturbation networks to connect ligands of interest. More specifically, ligand pairs with large dissimilarities should be avoided since they can lower convergence and decrease accuracy. Here, we propose a technique for automatic generation of intermediate molecules to break up problematic edges─calculations connecting two different ligands or molecules─into smaller perturbations. To this end, a modular tool was developed that generates intermediates for a molecule pair by enumerating R-group combinations calle

SUBMITTER: Schoenmaker L 

PROVIDER: S-EPMC11891892 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature