Publication: Extensive Molecular Dynamics simulations of the enzyme Catechol-O-Methyl Transferase: Methodological issues

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Title	Extensive Molecular Dynamics simulations of the enzyme Catechol-O-Methyl Transferase: Methodological issues
Authors/Editors*	A. Bunker, P.T. MÃ¤nnistÃ¶, J.-F. St.-Pierre, T. RÃ³g, P. Pomorski, M. Karttunen
Where published*	SAR and QSAR in Env. Res.
How published*	Journal
Year*	2007
Volume	19
Number
Pages	179-189
Publisher
Keywords	comt, parkinsons disease, molecular dynamics, drug-design
Link	http://dx.doi.org/10.1080/10629360701843318
Abstract	We report results from extensive 70\,ns all-atom molecular dynamics simulations of catechol-O-methyltransferase (COMT) enzyme. The simulations were performed with explicit TIP3P water and Mg2+ ions. Four different crystal structures of COMT, with and without different ligands, were used. These simulations are among the most extensive of thei kind and as such served as a stability test for such simulations. On the methodological side we found that the initial energy minimization procedure may be a crucial step: particular hydrogen bonds may break, and this can initiate an irreversible loss of protein structure that becomes observable in longer time scales of the order of tens of nanoseconds. This has important implications for both molecular dynamics and quantum mechanics--molecular mechanics simulations.