Wilcken, Rainer, Rodde, Stephane and Udvarhelyi, Aniko (2020) ReSCoSS: A Flexible Quantum Chemistry Workflow Identifying Relevant Solution Conformers of Drug-like Molecules. Journal of computer-aided molecular design.

Abstract

Conformational equilibria are at the heart of drug design, yet their energetic description is often hampered by the insufficient accuracy of low-cost methods. Here we present a flexible and semi-automatic workflow based on quantum chemistry, ReSCoSS, designed to identify relevant conformers and predict their equilibria across different solvent environments in the Conductor-like Screening Model for Real Solvents (COSMO-RS) framework. We demonstrate the utility and accuracy of the workflow through conformational case studies on several drug-like molecules from literature where relevant conformations are known. We further show that including ReSCoSS conformers significantly improves COSMO-RS based predictions of physicochemical properties over single-conformation approaches. ReSCoSS has found broad adoption in the in-house drug discovery and development work streams and has contributed to establishing quantum-chemistry methods as a strategic pillar in ligand discovery.

Item Type:	Article
Date Deposited:	29 Aug 2020 00:45
Last Modified:	29 Aug 2020 00:45
URI:	https://oak.novartis.com/id/eprint/42805