Contributions to the analysis of proteins
Name
764449130-MIT.pdf
Description
Full printable version
Size
15.75 MB
Format
Adobe PDF
Checksum (MD5)
ca6a1377ccda736504abc33d3e2e6227
Author(s)
Sharifi Sedeh, Reza
Advisor(s)
Klaus-Jürgen Bathe and Mark Bathe.
Date Issued
2011
Publisher
Massachusetts Institute of Technology
Abstract
Proteins 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.
Description
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2011.
Cataloged from PDF version of thesis.
Includes bibliographical references (p. 131-145).
Subjects
Mechanical Engineering.
MIT Department
Massachusetts Institute of Technology. Department of Mechanical Engineering
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