Our February miniWEBINAR topic was "Optimizing lead compounds with efficient binding free energy calculations", presented by Chris Neale, Principal Scientific Developer in the Affinity group at OpenEye, Cadence Molecular Sciences.
About this session:
Using our cloud-native modeling platform Orion®, we evaluate the accuracy and predictive utility of various methods for ranking ligands during lead optimization. Quantitative analysis shows that while rapid, high-throughput scoring methods can offer valuable insights, they are typically outperformed by more computationally intensive rescoring approaches, which are themselves generally surpassed by relative binding affinity predictions using nonequilibrium switching (NES). Direct comparison to other tools reveals that OpenEye NES provides robust guidance to classify molecules as high or low affinity across diverse aqueous protein targets. In addition to the inherent computational efficiency of NES, we demonstrate that computational investments can often be reduced by 75% while maintaining comparable accuracy in affinity predictions. These findings position OpenEye NES as a practical solution for lead optimization, offering substantial flexibility for computational chemists to balance accuracy and throughput effectively.
About presenter
Chris Neale, Ph.D., leads the molecular binding affinity prediction group at OpenEye, Cadence Molecular Sciences. His expertise and interests include method development for rational drug design, cell signaling via membrane proteins, uncertainty quantification, and task automation. Chris is also an editorial board member at the Biophysical Journal.
