Advanced Computational Strategies for Accurate Binding Affinity Predictions of RNA- & DNA-Targeting Small Molecules
- Predicting small-molecule binding affinities to nucleic acids remains a major computational challenge, hindering the development of new drugs that target them
- This study systematically evaluated the accuracy of a computational method called Free Energy Perturbation (FEP), using the FEP+ software and OPLS4 force field, to predict these binding affinities for over 100 ligands across eight diverse nucleic acid targets
- The FEP+ method demonstrated high accuracy, with results often close to experimental values (average error <1.4 kcal/mol or within one log unit of experimental accuracy), indicating that it is a reliable tool for guiding drug discovery programs targeting DNA and RNA