Use of essential and molecular dynamics to study gamma B-crystallin unfolding after non-enzymic post-translational modifications

Crabbe, M. J. C., Cooper, L. R. and Corne, D. W. (2003) Use of essential and molecular dynamics to study gamma B-crystallin unfolding after non-enzymic post-translational modifications. Computational Biology and Chemistry, 27 (4-5). pp. 507-510. ISSN 1476-9271 doi: 10.1016/s1476-9271(03)00048-3

Abstract/Summary

Essential and Molecular Dynamics (ED/MD) have been used to model the conformational changes of a protein implicated in a conformational disease-cataract, the largest cause of blindness in the world-after non-enzymic post-translational modification. Cyanate modification did not significantly alter flexibility, while the Schiff's base adduct produced a more flexible N-terminal domain, and intra-secondary structure regions, than either the cyanate adduct or the native structure. Glycation also increased linker flexibility and disrupted the charge network. A number of post-translational adducts showed structural disruption around Cys15 and increased linker flexibility; this may be important in subsequent protein aggregation. Our modelling results are in accord with experimental evidence, and show that ED/MD is a useful tool in modelling conformational changes in proteins implicated in disease processes. (C) 2003 Published by Elsevier Ltd.