Protein microenvironments for topology analysis

Amino Acid Residues are often the focus of research on protein structures. However, in a folded protein, each residue finds itself in an environment that is definedby the properties of its surrounding residues. The term microenvironment is usedherein to refer to these local ensembles. Not only do they have chemical properties but also topological properties which quantify concepts such as density,boundaries between domains and junction complexity. These quantifications areused to project a protein’s backbone structure into a series of scores.The hypothesis was that these sequences of scores can be used to discover proteindomains and motifs and that they can be used to align and compare groups of3D protein structures.This research sought to implement a system that could efficiently compute microenvironments such that they can be applied routinely to large datasets. Thecomputation of the microenvironments was the most challenging aspect in termsof performance, and the optimisations required are described.Methods of scoring microenvironments were developed to enable the extractionof domain and motif data without 3D alignment. The problem of allosteric sitedetection was addressed with a classifier that gave high rates of allosteric sitedetection.Overall, this work describes the development of a system that scales well withincreasing dataset sizes. It builds on existing techniques, in order to automatically detect the boundaries of domains and demonstrates the ability to processlarge datasets by application to allosteric site detection, a problem that has notpreviously been adequately solved.

Name dc:type.qualificationname

phd

Level dc:type.qualificationlevel

doctoral-pg

Grantor dc:publisher.institution

University of Strathclyde

Year dc:date.issued

2016

Author dc:creator

• Foley, Christopher Eric

Advisors dc:contributor.advisor

• Wilson, John
• Dufton, Mark

DOI

10.48730/vmb8-zb69

Identifier

T14464

Author Identifier

200956226

OAI identifier oai:identifier

oai:strathclyde:g445cd139