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Abstract #24279 Published in IGR 11-3
Effects of disease causing mutations on the essential motions in proteins
Achary MS; Nagarajaram HAJournal of Biomolecular Structure and Dynamics 2009; 26: 609-623
This study embodies a detailed comparative analysis of the essential motions of the Wild type and the eight different disease mutant forms of the Human CYP1b1. The mutations considered in this study have been implicated in Primary Congenital Glaucoma, an in-born, genetic disorder associated with eye-abnormality. The principal component analysis for Wild type and the Mutants was carried out using the stabilized molecular dynamics trajectories, which ranged from 35 to 45 nanoseconds. Investigations revealed the nature of the collective motions that characterize functionally relevant 'essential motions'. The essential motions in Wild type are characterized by the collective motions of the Substrate Access Channel including the (beta)-rich domain and the loops in the region of p450-reductase interaction. Comparative analysis of the essential motions of the Wild type and Mutants, especially those involving the functionally important regions indicated distinct differences in their magnitudes as well as the residue-wise distribution. The Mutants in general are associated with higher root mean square fluctuations, and involve some of the relatively intact core regions of the protein, in large collective motions. This study sheds light on the possible effects of disease causing mutations on the large functionally important collective motions in proteins.
Dr. M.S. Achary, Laboratory of Computational Biology, Centre for DNA Fingerprinting and Diagnostics (CDFD), Gruhakalpa Complex, Nampally Hyderabad, India
Classification:
3.4.2 Gene studies (Part of: 3 Laboratory methods > 3.4 Molecular genetics)
9.1.1 Congenital glaucoma, Buphthalmos (Part of: 9 Clinical forms of glaucomas > 9.1 Developmental glaucomas)
