Software Note: Use of essential and molecular dynamics to study γB-crystallin unfolding after non-enzymic post-translational modifications

  • Authors:

  • M.James C. Crabbe;Lee R. Cooper;David W. Corne

  • Affiliations:

  • School of Animal and Microbial Sciences, University of Reading, Whiteknights, Reading RG6 6AJ, UK;School of Animal and Microbial Sciences, University of Reading, Whiteknights, Reading RG6 6AJ, UK;Department of Computer Science, University of Reading, Whiteknights, Reading RG6 6AY, UK

  • Venue:
  • Computational Biology and Chemistry
  • Year:
  • 2003

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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.