Techniques for identifying long-range residue correlations in the fifth binding module of LDLR

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.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Electrical Engineering and Computer Science.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2006

Author dc:creator

• Lin, Jennifer W

Advisor dc:contributor.advisor

• Collin M. Schultz.

• Electrical Engineering and Computer Science.

Statement dc:rights

• 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.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/36808

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/36808