Multiscale Simulation Approaches to Understanding the Control of Trafficking in Cells

Philip Biggin

Biochemistry – University of Oxford

Multiscale Simulation Approaches to Understanding
the Control of Trafficking in Cells

Trafficking receptors control protein localisation through the recognition of specific signal sequences that specify unique cellular locations. Differences in luminal or organellular pH are important for the vectorial trafficking of cargo receptors. The KDEL receptor is responsible for maintaining the integrity of the ER by retrieving luminally localised folding chaperones in a pH-dependent mechanism. Structural studies have revealed the end states of KDEL receptor activation and the mechanism of selective cargo binding. However, precisely how the KDEL receptor responds to changes in luminal pH remains unclear. To address this key question of cell biology, we have used a combination of X-ray crystallography, cell-based assays and multi-scale simulation methods. In this talk I will discuss how we have used a variety of computational techniques including QM, GCMC, MD and coarse-grained MD to explain how this cellular trafficking works at the molecular level.

Konuşmacı hakkında

Philip Biggin is Professor of Computational Biochemistry in the Department of Biochemistry at the University of Oxford. He studied Computer-aided Chemistry at the University of Surrey for his undergraduate degree before completing a DPhil (PhD) in molecular biophysics at the University of Oxford. He then obtained a Wellcome Trust International Prize Fellowship that allowed him to undertake post-doctoral work at the Salk Institute, California. He returned to Oxford in 2000 for further post-doctoral work, before being awarded a prestigious RCUK Fellowship (with tenure track) in 2007. In 2012 this post reverted automatically to an Associate Professor (tenured). In 2016 he was made Full Professor at the University of Oxford.

His interests are focussed on the development and application of computational methods with particular respect to membrane proteins and membrane-drug interactions. He has over 150 peer-reviewed publications in this field, and has previously acted as a consultant to BioMedCentral. He served as Chair of the Molecular Graphics and Modelling Society for over 10 years and is a Fellow of the Royal Society of Chemistry (FRSC) as well as a chartered chemist (CChem). He is a member of the British Biophysical Society and the US Biophysical Society. He was a founder member of CCPBioSim and HECBioSim committees that aim to promote the application of high-performance computing to biological problems. He also chaired allocation panels on PRACE – the European supercomputing facility. He has also served on the REF panel, which is responsible for assessing the quality of UK science every seven years. His group has an excellent record in developing new approaches, from assessing conformational states via normal mode analysis, to a novel way to compare X-ray crystallographic data with molecular dynamics simulations and a way to align protein structures purely on the basis of their dynamics.