Computational Chemistry

Contact:
Dr John Wilkie
School of Chemistry
The University of Birmingham
Edgbaston, Birmingham
B15 2TT, United Kingdom

Email: informatics-crn-enquiries[at]cs.bham.ac.uk
Website: http://www.chem.bham.ac.uk/research/

Computational chemistry has an ever-increasing role to play in the understanding of enzyme catalysis and in the design of highly selective, tight-binding inhibitors. At Birmingham, we utilise molecular orbital theory (MO) and molecular mechanics (MM) calculations, in collaboration with synthetic medicinal chemists, to gain insight into the catalytic mechanisms of selected enzymes and thereby design selective inhibitors for them.

Phosphatase enzymes are of particular interest as one, Inositol Monophosphatase, is the target for lithium therapy in manic depression and appears to make use of a mechanism that differs from other phosphatase enzymes. We have made significant progress in refining our understanding of the catalytic mechanism and of the requirements for substrates and inhibitors so that we are currently in the process of designing inhibitors that can freely cross the blood-brain barrier. The design process is greatly simplified when the 3-dimensional structure of the target enzyme is known. We are also developing ideas in the design of mutations in enzyme active sites to change their substrate specificity.