Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.581710
Title: Improving the resolution of interaction maps : a middleground between high-resolution complexes and genome-wide interactomes
Author: Mora, Joan Segura
Awarding Body: University of Leeds
Current Institution: University of Leeds
Date of Award: 2013
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Abstract:
Protein-protein interactions are ubiquitous in Biology and therefore central to understand living organisms. In recent years, large-scale studies have been undertaken to describe, at least partially, protein-protein interaction maps or interactomes for a number of relevant organisms including human. Although the analysis of interaction networks is proving useful, current interactomes provide a blurry and granular picture of the molecular machinery, i.e. unless the structure of the protein complex is known the molecular details of the interaction are missing and sometime is even not possible to know if the interaction between the proteins is direct, i.e. physical interaction or part of functional, not necessary, direct association. Unfortunately, the determination of the structure of protein complexes cannot keep pace with the discovery of new protein-protein interactions resulting in a large, and increasing, gap between the number of complexes that are thought to exist and the number for which 3D structures are available. The aim of the thesis was to tackle this problem by implementing computational approaches to derive structural models of protein complexes and thus reduce this existing gap. Over the course of the thesis, a novel modelling algorithm to predict the structure of protein complexes, V-D2OCK, was implemented. This new algorithm combines structure-based prediction of protein binding sites by means of a novel algorithm developed over the course of the thesis: VORFFIP and M-VORFFIP, data-driven docking and energy minimization. This algorithm was used to improve the coverage and structural content of the human interactome compiled from different sources of interactomic data to ensure the most comprehensive interactome. Finally, the human interactome and structural models were compiled in a database, V-D2OCK DB, that offers an easy and user-friendly access to the human interactome including a bespoken graphical molecular viewer to facilitate the analysis of the structural models of protein complexes. Furthermore, new organisms, in addition to human, were included providing a useful resource for the study of all known interactomes.
Supervisor: Fernandez Fuentes, N. ; Jones, P. F. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.581710  DOI: Not available
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