Enabling In-Silico Hit Discovery Workflows Targeting RNA with Small Molecules

Abstract

In this study, we investigated and further improved the performance of SiteMap and Glide on predicting the binding site and ligand poses for ribonucleic acids (RNAs) receptors, achieving accuracy on par or better than the state of art benchmarks. Absolute binding free energy perturbation was also expanded to support RNA receptors, demonstrating strong correlation with experimental binding affinities on a diverse set. These advancements help pave a way forward for improved structure-based drug discovery targeting RNAs.