Quantum Chemical Modeling of Enzymatic Reactions: The Case of Histone Lysine Methyltransferase
2010 (English)In: Journal of Computational Chemistry, ISSN 0192-8651, E-ISSN 1096-987X, Vol. 31, no 8, 1707-1714 p.Article in journal (Refereed) Published
Quantum chemical cluster models of enzyme active sites are today an important and powerful tool in the study of various aspects of enzymatic reactivity. This methodology has been applied to a wide spectrum of reactions and many important mechanistic problems have been solved. Herein, we report a systematic study of the reaction mechanism of the histone lysine methyltransferase (HKMT) SET7/9 enzyme, which catalyzes the methylation of the N-terminal histone tail of the chromatin structure. In this study, HKMT SET7/9 serves as a representative case to examine the modeling approach for the important class of methyl transfer enzymes. Active site models of different sizes are used to evaluate the methodology. In particular, the dependence of the calculated energies on the model size, the influence of the dielectric medium, and the particular choice of the dielectric constant are discussed. In addition, we examine the validity of some technical aspects, such as geometry optimization in solvent or with a large basis set, and the use of different density functional methods.
Place, publisher, year, edition, pages
2010. Vol. 31, no 8, 1707-1714 p.
enzyme catalysis, density functional theory, methyltransferase
IdentifiersURN: urn:nbn:se:kth:diva-24819DOI: 10.1002/jcc.21458ISI: 000277483500016OAI: oai:DiVA.org:kth-24819DiVA: diva2:353458
QC 20100927. Uppdaterad från manuskript till artikel (20100927).2010-09-272010-09-272010-09-27Bibliographically approved