There is an urgent and unmet need for new drugs to treat major human diseases, including many types of cancer. NMR based methods in structure-based drug discovery are instrumental in characterising the complexes formed between target proteins and potential drug-like molecules.
Structural data drives rational modifications that optimise molecules to improve their drug-like properties, however this process largely ignores the effects of dynamics and allostery in the target protein. This project aims to develop new methodology to quantify the dynamic processes that effects small molecule binding to proteins, and to then use these methods to systematically analyse these dynamic processes and their influence on the drug development process.
Three relevant test systems have been chosen: Myeloid Cell Leukemia 1, the RAS binding domain of BRAF and Programmed Cell Death 4 (PDCD4). The mechanisms of allostery and the stabilising nature of small molecules is largely unknown and has never been explored.
Academic entry requirements: UK Bachelor Degree with at least 2:1 in a relevant subject or overseas equivalent.