Journal
JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN
Volume 35, Issue 4, Pages 399-415Publisher
SPRINGER
DOI: 10.1007/s10822-020-00337-7
Keywords
Conformations; Quantum chemistry; GFN-xTB; COSMO-RS; logP; ReSCoSS
Ask authors/readers for more resources
Conformational equilibria play a crucial role in drug design, but describing their energetics accurately can be challenging. A flexible and semi-automatic workflow called ReSCoSS, based on quantum chemistry, has been developed to identify relevant conformers and predict their equilibria in different solvent environments, improving predictions of physicochemical properties over single-conformation approaches in the COSMO-RS framework. This workflow has been widely adopted in drug discovery and development, establishing quantum chemistry methods as a strategic pillar in ligand discovery.
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. [GRAPHICS] .
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available