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We are using both bioinformatics and simulation-based approaches to help us understand the relationship between a proteins structure and protein dynamical behaviour in relation to function. Detailed, atomic-level information on protein internal motions can be determined using three main experimental methods: X-ray crystallography, nuclear magnetic resonance spectroscopy, and electron microscopy.
Participants
Summary
Protein internal motions can also be simulated using molecular dynamics methods. The different conformations observed from experiment or simulation provide us with detailed information about the internal rearrangements that occur when proteins function. These different conformations have been analysed using our DynDom program to create a database of domain movements in proteins (see https://dyndom.cmp.uea.ac.uk/dyndom/). In this database complex internal rearrangements in proteins are described in terms of the rigid-body movements of just a few dynamic domains.
With Prof. Stephen Laycock we are developing an interactive molecular docking tool, DockIT, that enables users to guide a drug molecule to its binding site in the protein receptor molecule. This tool, which is also VR enabled (see https://dockit.uk/), can be used in structure-based drug design and in education.
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Partners
Publications
[1] Hayward, Steven., Protein folding, protein dynamics and the topology of self-motions, R. Soc. Open Sci.11: 240873, DOIs: http://doi.org/10.1098/rsos.240873
[2] Hayward, Steven., A retrospective on the development of methods for the analysis of protein conformational ensembles, The Protein Journal. 42, 3, p. 181-191 11, 2023, DOIs: 10.1007/s10930-023-10113-9.
[3] Iakovou, Georgios., Laycock, Stephen, D. and Hayward, Steven., Interactive Flexible-Receptor Molecular Docking in Virtual Reality Using DockIT, Journal of Chemical Information and Modeling 2022 62 (23), 5855-5861. 2022, DOIs: https://doi.org/10.1021/acs.jcim.2c01274