Developing and applying computational methods to predict the interactions of small molecules with macromolecules.

Research

Our general research goal is to improve methods used for structure-based drug design and to apply these methods to design inhibitors for enzymes with biological relevance. A key point in our research is the interplay of theoretical and experimental methods.

Currently, we are working on the following points:

1. Drugs for neglected diseases We are involved in the tropical disease initiative at the University of Dundee.  We deal with all aspects of computational chemistry, in particular compound selection and structure-based ligand design.
2. Navigating chemical space. Several million unique compounds are available for screening from commercial suppliers.  Screening all of these compounds, virtually or experimentally, is not feasible.  Therefore, methods are needed to efficiently navigate chemical space in order to derive focused libraries or representative subsets.
3. Analysis of protein binding sites. Hit discovery programs are expensive.  Accordingly, it would be valuable to know how high the chance of finding a selective, drug-like inhibitor for a given target is before starting a campaign.  We are developing methods that can assist in this assessment.
4. Structure-based inhibitor design. In collaboration with other labs we are working on the structure-based design of inhibitors for a variety of targets.

Teaching

Publications

1. Mpamhanga CP, Spinks D, Tulloch LB, Shanks EJ, Robinson DA, Collie
IT, Fairlamb AH, Wyatt PG, Frearson JA, Hunter WN, Gilbert IH, Brenk R.
One Scaffold, Three Binding Modes: Novel and Selective Pteridine
Reductase 1 Inhibitors Derived from Fragment Hits Discovered by Virtual
Screening. J Med Chem 52 (14), 4454-65 (2009).

2. Brenk R, Schipani A, James D, Krasowski A, Gilbert IH, Frearson J,
Wyatt PG. Lessons Learnt from Assembling Screening Libraries for Drug
Discovery for Neglected Diseases. ChemMedChem 3 (3), 435-444 (2008). 

3. Brenk R, Vetter SW, Boyce SE, Goodin DB, Shoichet BK. Probing molecular
docking in a charged model binding site. J Mol Biol 357 (5), 1449-70
(2006).

4. Brenk R, Irwin JJ, Shoichet BK. Here be dragons: docking and screening
in an uncharted region of chemical space. J Biomol Screen 10 (7), 667-74
(2005).

For a full list of publications:
http://www.brenkgroup.dundee.ac.uk/publications.php