GROMOS-MD simulations on the coenzyme thiamin diphosphate in apoenzyme environment

✍ Scribed by Rudolf Friedemann; Anne Von Fircks; Stefan Naumann

• Book ID: 101253051
• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 234 KB
• Volume: 70
• Category: Article
• ISSN: 0020-7608
• DOI: 10.1002/(sici)1097-461x(1998)70:2<407::aid-qua18>3.0.co;2-8

✦ Synopsis

Thiamin diphosphate ThDP is an essential cofactor for a number of Ž . enzymes, especially of pyruvate decarboxylase PDC which catalyzes the decarboxylation of ␣-keto acids. Recently, the crystal structure of PDC-bound ThDP has been determined. Ž . 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 ẘith a cut-off radius less than 8.5 A 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.