Understanding the structure and dynamics of the collagen triple helix is critical to un- derstanding the effect of mutations that arise in connective tissue and to understanding its interactions with receptors. Defects in triple helix domain of collagen have been associated with a number of human collagen diseases. Osteogenesis Imperfecta (OI) characterized by brittle bones affects roughly one in 10,000 individuals and results from mutations in type I collagen. The severity of the disease varies widely, ranging from mild to lethal cases. The molecular basis of the disease is still not understood. Here we integrate computational ap- proaches and NMR experiments to provide insight into the effects of variations in amino acid sequence on the conformation and dynamics of the collagen triple helix using colla- gen model peptides (CMPs), and to provide a molecular interpretation of several types of NMR experiments. Theoretical calculations of quantum mechanical NMR chemical shifts on the MD selected snapshots represent the first example of a reasonable fit of experimental data and highlight the sensitivity of the NH chemical shift to the complex dynamics of the H-bonds. The degree of inter-chain hydrogen bonding and the dynamics with different G-X-Y triplets are considered important for collagen recognition and binding sites containing disease-related mutation. A analysis of dynamics of triple helix have been studied using 15N relaxation measurements and model-free approach. This work is one of the first detailed MD studies of NMR relaxation data for proteins with high shape anisotropy. We interpret 15N relaxation measurements arising from the a variety of types of motions in the triple helical peptides. Both molecular dynamics simulations and analyses of NMR data have pointed to significant amounts of bending and twisting motions existing in the triple helical peptide, and we compare collagen-like peptides to other deformable rod-like molecules such as DNA duplexes. A Weakly Bending Rod (WBR) model is introduced to mimic the elastic properties of these flexible rod-like CMPs and provide insight into the interpretation of the relaxation data and order parameter profiles.
Subject (authority = RUETD)
Topic
Computational Biology and Molecular Biophysics
Subject (authority = ETD-LCSH)
Topic
Collagen diseases
Subject (authority = ETD-LCSH)
Topic
Osteogenesis imperfecta
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_6028
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
1 online resource (xxii, 125 p. : ill.)
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Note (type = statement of responsibility)
by Iwen Fu
RelatedItem (type = host)
TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier (type = local)
rucore19991600001
Location
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
Rutgers University. Graduate School - New Brunswick
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License
Name
Author Agreement License
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