PhD project:

Computing Aqueous Solubility and Understanding Hydrophobicity


Dr John Mitchell, Biomolecular Sciences, University of St Andrews


Dr Tanja van Mourik, Chemistry, University of St Andrews

funding details:

Competition Funded Project - UK/EU Students only

closing date:

31 Mar 2010

Contact: 01334 467259

The project will develop new methods of calculating the aqueous solubility of organic molecules. Its philosophy is to compute all the relevant solute-solute, solute-solvent, and solvent-solvent enthalpy and entropy terms. This must be done both for the initial state, pure water and the solute in its lowest free energy crystalline state, and also for the final state, the solution. We have previously developed models that combine a theoretically rigorous treatment of the crystalline state with a description of the aqueous solution that incorporates empirical structure-property relationships. We intend to expand on this work, widening its applicability, and especially to develop its biochemical relevance. In particular, we will develop a model that is capable of systematic improvement by partitioning the free energy of solvation into a number of distinct and physically meaningful enthalpic and entropic components. This will include more accurate computation of the solute-solvent interaction.

Its primary practical applications involve in silico virtual screening of molecules for drug discovery. The work will also be of value, however, in improving our understanding of the molecular basis of the hydrophobic effect. Such knowledge can be used in diverse areas, for instance modelling protein folding, predicting the blood-brain partitioning of pharmaceuticals, and computing protein-ligand binding affinities.