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dc.contributor.advisorKlaus-Jürgen Bathe and Mark Bathe.en_US
dc.contributor.authorSharifi Sedeh, Rezaen_US
dc.contributor.otherMassachusetts Institute of Technology. Dept. of Mechanical Engineering.en_US
dc.date.accessioned2011-12-09T21:30:16Z
dc.date.available2011-12-09T21:30:16Z
dc.date.copyright2011en_US
dc.date.issued2011en_US
dc.identifier.urihttp://hdl.handle.net/1721.1/67599
dc.descriptionThesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2011.en_US
dc.descriptionCataloged from PDF version of thesis.en_US
dc.descriptionIncludes bibliographical references (p. 131-145).en_US
dc.description.abstractProteins are essential to organisms and play a central role in almost every biological process. The analysis of the conformational dynamics and mechanics of proteins using numerical methods, such as normal mode analysis (NMA), provides insight into their functional mechanisms. However, despite the fact that much effort has been focused on improving NMA over the last few decades, the analysis of large-scale protein motions is still infeasible due to computational limitations. In this work, first, we identify the usefulness and effectiveness of the subspace iteration (SSI) procedure, otherwise widely used in structural engineering, for the analysis of proteins. We also develop a novel technique for the selection of iteration vectors in protein NMA, which significantly increases the effectiveness of the method. The SSI procedure also lends itself naturally to efficient NMA of multiple neighboring macromolecular conformations, as demonstrated in a conformational change pathway analysis of adenylate kinase. Next, we present a new algorithm to account for the effects of solvent-damping on slow protein conformational dynamics. The algorithm proves to be an effective approach to calculating the diffusion coefficients of proteins with various molecular weights, as well as their Langevin modes and corresponding relaxation times, as demonstrated for the small molecule crambin. Finally, the structure of Homo sapiens fascin-1, an actin-binding protein that is present predominantly in filopodia, is examined and described in detail. Application of a sequence conservation analysis to the protein indicates highly conserved surface patches near the putative actin-binding domains of fascin. A novel conformational dynamics analysis suggests that these domains are coupled via an allosteric mechanism that may have important functional implications for F-actin bundling by fascin.en_US
dc.description.statementofresponsibilityby Reza Sharifi Sedeh.en_US
dc.format.extent145 p.en_US
dc.language.isoengen_US
dc.publisherMassachusetts Institute of Technologyen_US
dc.rightsM.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.en_US
dc.rights.urihttp://dspace.mit.edu/handle/1721.1/7582en_US
dc.subjectMechanical Engineering.en_US
dc.titleContributions to the analysis of proteinsen_US
dc.typeThesisen_US
dc.description.degreePh.D.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Mechanical Engineering
dc.identifier.oclc764449130en_US


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