Improved methods to encode molecular activity with shape and polarity (CASE Studentship)
Principal investigator(s): Dr Jim Warwicker
Funding: Funding available for eligible UK/EU applicants.
Subject Areas
- Biochemistry
- Bioinformatics
- Biomolecular Sciences
- Biotechnology
- Pharmacology
- Structural Biology
Description
Shape and charge are key determinants in describing the relationships between small molecules of pharmaceutical relevance, and are therefore important in drug design and virtual screening processes. The same properties also describe many features of proteins and other biological macromolecules. This may simply be as a complementary surface to a drug-like molecule, but also includes the chemical underpinning of biological processes such as catalysis by enzymes. This collaborative PhD is between the groups of Andrew Grant at the Alderley Park site of AstraZeneca, and Jim Warwicker at the University of Manchester. Both groups are active in developing methods for computing solvation properties, either a tool to aid drug design or as a probe to understand biological processes.
This project will run between the two groups to improve techniques by learning from these related project areas. For example, can the tools used to cluster drug-like molecules also be used to classify macromolecules? Conversely, could a knowledge of catalysis in terms of shape and charge, aid inhibitor design? Where the therapeutic molecules are themselves macromolecules, antibodies for example, which are the most appropriate methods for modelling interactions with a receptor?
The student will benefit from interactions within a computational chemistry environment at AstraZeneca that is directed ultimately towards pharmaceutical discovery, and from a background grouping at Manchester with bioinformatics and systems biology components. This PhD is computational, with substantial resource (e.g. computer clusters, databases) at both sites.
Related Publications
- The SAMP1 Solvation Challenge: Further Lessons Regarding the Pitfalls of Parametrization. (2009) Nicholls A, Wlodek S, Grant JA. J Phys Chem B 113:4521-4532
- Sequence and structural features of enzymes and their active sites by EC class. (2009) Bray T, Doig AJ, Warwicker J. J Mol Biol 386:1423-1436
- Volume-based solvation models out-perform area-based models in combined studies of wild-type and mutated protein-protein interfaces. (2008) Bougouffa S, Warwicker J. BMC Bioinformatics 9:448
- Molecular shape and electrostatics in the encoding of relevant chemical information. Nicholls A, Grant JA (2005) Comput Aided Mol Des 19:661-686
How to apply
Find out How to apply for this PhD Project.