The interface between biology and chemistry is fertile ground for the development of new computational techniques. Yet it is still hard to predict protein-ligand binding, model protein folding or design effective pharmaceutical products.
Enzyme-catalysed reactions are ubiquitous and essential to the chemistry of life. Structures, gene sequences, mechanisms, metabolic pathways and kinetic data are currently spread between many different databases and throughout the literature. We have created MACiE, the world's first comprehensive electronic database of the chemical mechanisms of enzymatic reactions. We are using MACIE to investigate fundamental questions about the chemistry of enzyme functions, their evolution, and their substrate specificity.
Improving the prediction of solubility is essential to reduce the current unacceptable attrition rate in drug development. We are developing methods to predict aqueous solubility for drug-like molecules, and hope to move on to study its dependence on pH, salt effects and crystal polymorphism. We have developed a number of predictive methods for solubility, of which the most successful is based on a Random Forest of decision trees. We are also using computational chemistry to calculate the various energy terms associated with solvation. This work spans quantum chemistry, molecular simulation, QSAR and chemical informatics.
Additional information about the current Mitchell Group can be found here: http://chemistry.st-andrews.ac.uk/staff/jbom/group/
Ph.D. studentships in Modelling the Evolution of Enzyme Catalysis and Computing Aqueous Solubility and Understanding Hydrophobicity are now available.
Selected Recent Publications
DS Palmer, A Llinàs, I Morao, GM Day, JM Goodman, RC Glen & JBO Mitchell, Molecular Pharmaceutics, (2008), 5, 266-279
NM O'Boyle, GL Holliday, DE Almonacid & JBO Mitchell, Journal of Molecular Biology, (2007), 368, 1484-1499
GL Holliday, DE Almonacid, GJ Bartlett, NM O'Boyle, JW Torrance, P Murray-Rust, JBO Mitchell & JM Thornton, Nucleic Acids Research, (2007), 35, D515-D520
GL Holliday, DE Almonacid, JBO Mitchell & JM Thornton, Journal of Molecular Biology, (2007), 372, 1261-1277
DS Palmer, NM O'Boyle, R C Glen & JBO Mitchell, Journal of Chemical Information and Modeling, (2007), 47, 150-158