Developing physics-based methods for predicting physico-chemical properties required in pharmaceutical drug discovery and manufacturing

Dr David Palmer and Daniel Fowles, in the department of Pure and Applied Chemistry at the University of Strathclyde are using ARCHIE-WeSt to develop new physics-based methods of predicting physico-chemical properties that are important for drug discovery and manufacturing. Current drug design procedures utilise cheminformatics and machine-learning based methods to predict physico-chemical properties of drug like molecules. Although these methods are powerful, they offer only limited insights into the chemical processes that they are predicting. By developing new physics-based approaches, we aim to replace these informatics-based methods with a more information-rich alternative. This physics-based approach will be capable of following a potential drug molecule through a chemical process, providing a detailed description of the underlying chemistry. The development of a physics-based approach has already proved successful. In a recent collaboration with the University of St Andrews and University College London, we developed proof-of-concept of a physics-based method for predicting intrinsic aqueous solubility of drug-like molecules through a thermodynamic cycle [J. Chem. Theory Comput. 2021, 17, 6, 3700–3709].We aim to further develop this method and expand the scope of the project to the solvation thermodynamics of non-aqueous solvent in 3DRISM (3D Reference Interaction Site Model).