title: Protein Complexes Structure Prediction by Combination of Binary Interactions Derived by Homology
creator: Pichaud, Matthieu
subject: ddc-570
subject: 570 Life sciences
description: Proteins are key participants in most cellular processes. However, they rarely function in isolation and usually they form multimolecular assemblies. The structural description of such an assembly provides critical details about the protein function. As the determination of such structures remains a great experimental challenge, only a small fraction of known protein complexes are currently available. This has created a need for alternative, predictive methods that can bridge the gap between complexes that are known to exist in the cell, and those for which structural information is available.    This thesis presents a program to predict the structure of protein assemblies from the structures of their subunits. The method combines predictions of pairwise arrangements derived from homologous interaction templates to consider all possible assemblies. The problem of finding the best arrangement is modeled as a graph to allow fast graph traversing algorithms to be exploited. Individual predictions are evaluated by sequence identity or structural similarity between the subunits and the templates or by evaluation of the interfaces in the predictions. The method is benchmarked on three-domain assemblies derived from known structures and on nine complete structures that could possibly be re-assembled in a non-trivial fashion from previously determined structures. The method was also applied to complexes determined from high-throughput complex determination procedures, including RNA polymerase I and the Cdc48/Ufd1/Npl4 complex from the ubiquitin-proteasome pathway.    The benchmark demonstrates that the approach can often work on small assemblies. For larger complexes, certain details can be predicted, and occassionaly large parts of the complex, though currently a lack of suitable templates limits applicability. Nevertheless, the method can now be applied to any protein complex and should be particularly useful when structures are difficult to obtain by experiments, and where additional information, such as pairwise interactions or stoichiometry, is available.  
date: 2008
type: Dissertation
type: info:eu-repo/semantics/doctoralThesis
type: NonPeerReviewed
format: application/pdf
identifier: https://archiv.ub.uni-heidelberg.de/volltextserverhttps://archiv.ub.uni-heidelberg.de/volltextserver/8892/1/Thesis_allcollected8.pdf
identifier: DOI:10.11588/heidok.00008892
identifier: urn:nbn:de:bsz:16-opus-88929
identifier:   Pichaud, Matthieu  (2008) Protein Complexes Structure Prediction by Combination of Binary Interactions Derived by Homology.  [Dissertation]     
relation: https://archiv.ub.uni-heidelberg.de/volltextserver/8892/
rights: info:eu-repo/semantics/openAccess
rights: http://archiv.ub.uni-heidelberg.de/volltextserver/help/license_urhg.html
language: eng