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Collin M. Schultz. Lin, Jennifer W Massachusetts Institute of Technology. Dept. of Electrical Engineering and Computer Science. Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science 2007-03-12T17:55:41Z 2007-03-12T17:55:41Z 2006 2006 http://hdl.handle.net/1721.1/36808 80778749 Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2006. Includes bibliographical references (p. 87-90). The study of correlations between residues in distal regions of a protein structure may provide insights into the mechanism of protein folding. Such long-range correlations may exist between distant residues that are conserved by evolution or physically related by motion. Two computational approaches, one involving hidden Markov models (HMMs) and the other applying molecular dynamics (MD), were implemented to identify a comprehensive set of residue couplings, as well as provide possible explanations for the correlations. HMMs were employed to model the secondary structural elements of proteins in order to discover residues correlated by coevolution. MD simulations and cross-correlation analyses were performed to determine residues coupled by motion. The protein system that was chosen for the study of long-range correlated residues was the fifth binding module (LR5) of the low-density lipoprotein receptor (LDLR) which regulates the cholesterol level in the bloodstream. (cont.) The LR5 repeat is crucial to the binding of LDLR to lipoprotein particles that carry cholesterol. The HMM and MD approach identified correlations between residues that have been postulated to bind to a particular type of lipoprotein and residues involved in calcium ion coordination which maintains the folding of the LDLR structure. Energetic pathways of the LR5 module were constructed to provide insights into structural stability and functional importance of the residue couplings. by Jennifer W. Lin. M.Eng. 90 p. eng Massachusetts Institute of Technology M.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. http://dspace.mit.edu/handle/1721.1/7582 Electrical Engineering and Computer Science. Techniques for identifying long-range residue correlations in the fifth binding module of LDLR Thesis application/pdf false Publication unknown unknown <Publication xmlns="https://www.openaire.eu/cerif-profile/1.1/" id="aa4d0922-fcf6-4806-bdf9-9a44402a382e"> <Type xmlns="https://www.openaire.eu/cerif-profile/vocab/COAR_Publication_Types">http://purl.org/coar/resource_type/c_1843</Type> <Language>eng</Language> <Title>Techniques for identifying long-range residue correlations in the fifth binding module of LDLR</Title> <PublishedIn> <Publication> </Publication> </PublishedIn> <PublicationDate>2006</PublicationDate> <Authors> <Author> <DisplayName>Lin, Jennifer W</DisplayName> <Affiliation> <OrgUnit> </OrgUnit> </Affiliation> </Author> </Authors> <Editors> </Editors> <Publishers> <Publisher> <DisplayName>Massachusetts Institute of Technology</DisplayName> <OrgUnit /> </Publisher> </Publishers> <License>http://dspace.mit.edu/handle/1721.1/7582</License> <Keyword>Electrical Engineering and Computer Science.</Keyword> <Abstract>The study of correlations between residues in distal regions of a protein structure may provide insights into the mechanism of protein folding. Such long-range correlations may exist between distant residues that are conserved by evolution or physically related by motion. Two computational approaches, one involving hidden Markov models (HMMs) and the other applying molecular dynamics (MD), were implemented to identify a comprehensive set of residue couplings, as well as provide possible explanations for the correlations. HMMs were employed to model the secondary structural elements of proteins in order to discover residues correlated by coevolution. MD simulations and cross-correlation analyses were performed to determine residues coupled by motion. The protein system that was chosen for the study of long-range correlated residues was the fifth binding module (LR5) of the low-density lipoprotein receptor (LDLR) which regulates the cholesterol level in the bloodstream.</Abstract> <Abstract>(cont.) The LR5 repeat is crucial to the binding of LDLR to lipoprotein particles that carry cholesterol. The HMM and MD approach identified correlations between residues that have been postulated to bind to a particular type of lipoprotein and residues involved in calcium ion coordination which maintains the folding of the LDLR structure. Energetic pathways of the LR5 module were constructed to provide insights into structural stability and functional importance of the residue couplings.</Abstract> <Access xmlns="http://purl.org/coar/access_right" > </Access> </Publication>