Computational Investigations of Protein Domain Movements (HAYWARD_U15SF)

This PhD project is offered on a self-funding basis. It is open to applicants with funding or those applying to funding sources. Details of tuition fees can be found at www.uea.ac.uk/pgresearch/pgrfees. 

A bench fee is also payable on top of the tuition fee to cover specialist equipment or laboratory costs required for the research. The amount charged annually will vary considerably depending on the nature of the project and applicants should contact the primary supervisor for further information about the fee associated with the project.

Description

Protein domain movements are often engaged for protein function (ref(i)). The classic view has a functional ligand bind to the protein in the interdomain cleft upon which closure occurs via a domain movement trapping the ligand. There are two main ways to study protein domain motions computationally: by analysis of the existing structures in the Protein Data Bank (PDB), or by performing simulations. Using the former approach we have recently developed a graph representation (ref(ii)) of a domain movement based on changes in contacts between amino-acid residues. This “Dynamic Contact Graph” provides new insights by identifying key residues involved in the domain closure process. The graphs also provide visual metaphors for the kinds of movements that the residues undergo so indicating their possible role in the movement. This PhD project will involve the development of the Dynamic Contact Graph methodology for application to the results of our new DynDom3D software (ref(iii)) which is able to analyse domain movements in large multimeric proteins where allosteric mechanism may play a role. It is expected that the application of these powerful tools will lead to further insights into the mechanisms of protein domain closure and to new ways to classify protein domain movements. These findings will have implications for the understanding of biochemical processes in the cell as well as drug design (ref(iv)). For more information on protein domain movements, methodologies for their study, databases, etc, see our website: www.cmp.uea.ac.uk/dyndom.

Nr of positions available : 1