| 1. |
- Carvalho, Alexandra T P, et al.
(författare)
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Challenges in computational studies of enzyme structure, function and dynamics
- 2014
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Ingår i: Journal of Molecular Graphics and Modelling. - : Elsevier BV. - 1093-3263 .- 1873-4243. ; 54, s. 62-79
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Forskningsöversikt (refereegranskat)abstract
- In this review we give an overview of the field of Computational enzymology. We start by describing the birth of the field, with emphasis on the work of the 2013 chemistry Nobel Laureates. We then present key features of the state-of-the-art in the field, showing what theory, accompanied by experiments, has taught us so far about enzymes. We also briefly describe computational methods, such as quantum mechanics-molecular mechanics approaches, reaction coordinate treatment, and free energy simulation approaches. We finalize by discussing open questions and challenges.
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| 2. |
- Doron, Dvir, et al.
(författare)
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How Accurate Are Transition States from Simulations of Enzymatic Reactions?
- 2014
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Ingår i: Journal of Chemical Theory and Computation. - : American Chemical Society (ACS). - 1549-9618 .- 1549-9626. ; 10:5, s. 1863-1871
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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