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dc.contributor.advisorIm, Wonpil
dc.contributor.authorRui, Huan
dc.date.accessioned2014-06-18T04:57:12Z
dc.date.available2014-06-18T04:57:12Z
dc.date.issued2013-05-31
dc.date.submitted2013
dc.identifier.otherhttp://dissertations.umi.com/ku:12719
dc.identifier.urihttp://hdl.handle.net/1808/14217
dc.description.abstractProteins are among the four unique organic constituents of cells. They are responsible for a variety of important cell functions ranging from providing structural support to catalyzing biological reactions. They vary in shape, dynamic behavior, and localization. All of these together determine the specificity in their functions, but the question is how. The ultimate goal of the research conducted in this thesis is to answer this question. Two types of proteins are of particular interest. They include transmembrane proteins and protein assemblies. Using computer simulations with available experimental data to validate the simulation results, the research described here aims to reveal the structure and dynamics of proteins in their native-like environment and the indication on the mechanism of their functions. The first part of the thesis focuses on studying the structure and functions of transmembrane proteins. These proteins are consisted of transmembrane α-helices or β-strands, and each of the secondary structure elements adopts a unique orientation in the membrane following its local interactions. The structure of the entire protein is a collection of the orientations of these elements and their relative positions with respect to one another. These two basic aspects of membrane protein structure are studied in Chapter II and III. In Chapter II, efforts are given to determine the favorable orientation of a β-hairpin peptide, protegrin-1, in different lipid bilayers. The orientational preference results from the interplay between the protein and the surrounding lipid molecules. Chapter III is centered on revealing the structure and dynamics of caveolin-1 in DMPC bilayers. Caveolin-1 forms a re-entrant helix-turn-helix structure with two α-helices embedded in the membrane bilayer. The study shows that caveolin-1 monomer is rather dynamic and maintains its inserted conformation via both specific and non-specific protein-lipid interactions. To investigate the structural and dynamic impact on the function of a membrane protein, molecular dynamics simulations of the voltage-dependent anion channel are performed and the results are presented in Chapter IV. It is found in this chapter that the electrostatic interactions between charged residues on the channel wall facing the lumen are responsible for retarding the cation current, therefore giving the channel its anion selectivity. The second category of protein that is of interest in this thesis is the assembled protein complex, especially the ones that are highly symmetric. Actually, many membrane proteins belong to this category as well, but the study presented here in Chapter V involves simulations performed on a soluble protein complex, bacterioferritin B from Pseudomonas Aeruginosa. It is revealed by the simulations that the dynamic behavior of the protein is magnified by the symmetry and is tightly associated to its function.
dc.format.extent195 pages
dc.language.isoen
dc.publisherUniversity of Kansas
dc.rightsThis item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
dc.subjectBioinformatics
dc.subjectBiophysics
dc.subjectBiochemistry
dc.subjectMembrane bilayers
dc.subjectMembrane protein
dc.subjectMolecular dynamics simulations
dc.subjectProtein assembly
dc.subjectProtein dynamics
dc.titleComputational Studies of Protein Structure, Dynamics, and Function in Native-like Environments
dc.typeDissertation
dc.contributor.cmtememberDeeds, Eric
dc.contributor.cmtememberKaranicolas, John
dc.contributor.cmtememberRivera, Mario
dc.contributor.cmtememberVakser, Ilya
dc.thesis.degreeDisciplineBiochemistry & Molecular Biology
dc.thesis.degreeLevelPh.D.
kusw.bibid8086141
dc.rights.accessrightsopenAccess


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