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Title: The evolution of protein structure
Author: Williams, Simon
ISNI:       0000 0001 2429 9906
Awarding Body: University of Manchester
Current Institution: University of Manchester
Date of Award: 2008
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The complex constraints imposed by protein structure and function result in varied rates of sequence and structural divergence in proteins. Analysis of sequence differences between homologous proteins can advance our understanding of structural divergence and some of the constraints that govern the evolution of these molecules. It is likely that with further understanding of evolutionary constraints, accurate predictions of both past and future protein evolution may be possible. In this thesis I examine the relationship between amino acid sequence and structural divergence. Firstly, I demonstrate that the relationship between protein sequence and structural divergence is complex and likely to be governed by a variety of evolutionary constraints, resulting in different degrees of divergence in different local structural environments. Secondly, compensatory substitutions are not found to be widespread and instead subtle. structural divergence is associated with sequence change. Thirdly, by utilising a basic model of structural constraint along with probabilities of substitutions occurring in different positions, I show that accurate predictions can be made of sequence diversity observed within a protein family. This model, when applied to the design of a hypothetical polyvalent HIV vaccine, can remove improbable sequence variation and reduce the number of sequence constructs required for optimal coverage.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available