Type I collagen is a fibrous protein which is commonly used in the human body for structural and functional integrity. Mutations in the alpha(1) and alpha(2) chains of this triple-helical protein induce the disease osteogenesis imperfecta (OI). OI is expressed in people by a number of phenotypes ranging from a disease process that is lethal in utero to one that is only detected through gene analysis. We are using the techniques of molecular dynamics and free energy perturbation to predict the phenotypic severity that result from single point mutations of type I collagen. In particular, we are focusing on the following three issues in our investigation: 1) evaluation and, if necessary, the development of a molecular mechanic force field to study fibrous proteins; 2) determination of protein and water-protein structural changes induced by single point mutations of type I collagen. 3) determination of changes in stability between native collagen fragments and collagen fragments in which a single point mutation has occurred.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR001081-19
Application #
5222446
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
19
Fiscal Year
1996
Total Cost
Indirect Cost
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