Change search
ReferencesLink to record
Permanent link

Direct link
How Accurate Are Transition States from Simulations of Enzymatic Reactions?
Umeå University, Faculty of Science and Technology, Department of Chemistry.
2014 (English)In: Journal of Chemical Theory and Computation, ISSN 1549-9618, E-ISSN 1549-9626, Vol. 10, no 5, 1863-1871 p.Article in journal (Refereed) Published
Abstract [en]

The rate expression of traditional transition state theory (TST) assumes no recrossing of the transition state (TS) and thermal quasi-equilibrium between the ground state and the TS. Currently, it is not well understood to what extent these assumptions influence the nature of the activated complex obtained in traditional TST-based simulations of processes in the condensed phase in general and in enzymes in particular. Here we scrutinize these assumptions by characterizing the TSs for hydride transfer catalyzed by the enzyme Escherichia coli dihydrofolate reductase obtained using various simulation approaches. Specifically, we compare the TSs obtained with common TST-based methods and a dynamics-based method. Using a recently developed accurate hybrid quantum mechanics/molecular mechanics potential, we find that the TST-based and dynamics-based methods give considerably different TS ensembles. This discrepancy, which could be due equilibrium solvation effects and the nature of the reaction coordinate employed and its motion, raises major questions about how to interpret the TSs determined by common simulation methods. We conclude that further investigation is needed to characterize the impact of various TST assumptions on the TS phase-space ensemble and on the reaction kinetics.

Place, publisher, year, edition, pages
2014. Vol. 10, no 5, 1863-1871 p.
National Category
Chemical Sciences
URN: urn:nbn:se:umu:diva-90781DOI: 10.1021/ct5000742ISI: 000336020400005OAI: diva2:754155
Available from: 2014-10-09 Created: 2014-07-01 Last updated: 2014-10-09Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Nam, Kwangho
By organisation
Department of Chemistry
In the same journal
Journal of Chemical Theory and Computation
Chemical Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 151 hits
ReferencesLink to record
Permanent link

Direct link