title: Use of essential and molecular dynamics to study gammaB-crystallin unfolding after non-enzymic post-translational modifications.
abstract: 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.
authors.affiliation: School of Animal and Microbial Sciences, University of Reading, Reading RG6 6AJ, Whiteknights, UK
authors.forename: M James C
authors.initials: MJ
authors.lastname: Crabbe
authors.forename: Lee R
authors.initials: LR
authors.lastname: Cooper
authors.forename: David W
authors.initials: DW
authors.lastname: Corne
mesh_terms: D003198:Computer Simulation; D008958:Models, Molecular; D017510:Protein Folding; D011499:Protein Processing, Post-Translational; D017433:Protein Structure, Secondary; D038222:gamma-Crystallins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D038222:gamma-Crystallins