ISSN:
0020-7608
Keywords:
molecular dynamics
;
hydrogen bonding
;
conformational studies
;
Chemistry
;
Theoretical, Physical and Computational Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
Thiamin diphosphate (ThDP) is an essential cofactor for a number of enzymes, especially of pyruvate decarboxylase (PDC) which catalyzes the decarboxylation of α-keto acids. Recently, the crystal structure of PDC-bound ThDP has been determined. Based on these X-ray data molecular dynamics (MD) simulations of the isolated coenzyme as well as of ThDP in its enzymatic environment were performed, using the GROMOS87 software package. In the ThDP-apoenzyme model all significant amino acid residues with a cut-off radius less than 8.5 Å from the cofactor were considered. The conformational behavior and the formation of specific structures of both ThDP and enzyme-bound ThDP were investigated in order to get hints on the activity and the mechanism of the coenzyme. Therefore, trajectories of significant structural parameters were analyzed by our graphics tool. Moreover, Ramachandran-like plots with respect to significant torsion angles were used for the illustration. Finally, MD simulations on ThDP analogs with less or none catalytic activity and apoenzyme mutants were included, in order to study the cofactor-apoenzyme binding. © 1998 John Wiley & Sons, Inc. Int J Quant Chem 70: 407-413, 1998
Additional Material:
8 Ill.
Type of Medium:
Electronic Resource
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