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GROMOS‐MD simulations on the coenzyme thiamin diphosphate in apoenzyme environment
Author(s) -
Friedemann Rudolf,
Von Fircks Anne,
Naumann Stefan
Publication year - 1998
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/(sici)1097-461x(1998)70:2<407::aid-qua18>3.0.co;2-8
Subject(s) - cofactor , chemistry , decarboxylation , enzyme , ramachandran plot , stereochemistry , coenzyme a , thiamine , molecular dynamics , computational chemistry , protein structure , catalysis , biochemistry , reductase
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