How Important Are Quantum Mechanical Nuclear Motions in Enzyme Catalysis?

1996 ◽  
Vol 118 (47) ◽  
pp. 11745-11751 ◽  
Author(s):  
Jenn-Kang Hwang ◽  
Arieh Warshel
Keyword(s):  
Enzyme Catalysis ◽  
Quantum Mechanical

scholarly journals Revealing quantum mechanical effects in enzyme catalysis with large-scale electronic structure simulation

2019 ◽  
Vol 4 (2) ◽  
pp. 298-315 ◽  
Author(s):  
Zhongyue Yang ◽  
Rimsha Mehmood ◽  
Mengyi Wang ◽  
Helena W. Qi ◽  
Adam H. Steeves ◽  
...  
Keyword(s):  
Electronic Structure ◽  
Enzyme Catalysis ◽  
Active Sites ◽  
Large Scale ◽  
Quantum Mechanical ◽  
Length Scales ◽  
Mechanical Simulation ◽  
Mechanical Effects ◽  
Structure Simulation ◽  
Quantum Mechanical Effects

Large scale quantum mechanical simulation systematically reveals length scales over which electronically driven interactions occur at enzyme active sites.

scholarly journals Barrier Compression and Its Contribution to Both Classical and Quantum Mechanical Aspects of Enzyme Catalysis

2010 ◽  
Vol 98 (1) ◽  
pp. 121-128 ◽  
Author(s):  
Sam Hay ◽  
Linus O. Johannissen ◽  
Michael J. Sutcliffe ◽  
Nigel S. Scrutton
Keyword(s):  
Enzyme Catalysis ◽  
Quantum Mechanical

scholarly journals Enzyme Models—From Catalysis to Prodrugs

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3248
Author(s):  
Zeinab Breijyeh ◽  
Rafik Karaman
Keyword(s):  
Tranexamic Acid ◽  
Physicochemical Properties ◽  
Experimental Research ◽  
Enzyme Catalysis ◽  
Antibacterial Agents ◽  
Minimum Energy ◽  
Cefuroxime Axetil ◽  
Quantum Mechanical ◽  
Enzymatic Reactions ◽  
Enzyme Models

Enzymes are highly specific biological catalysts that accelerate the rate of chemical reactions within the cell. Our knowledge of how enzymes work remains incomplete. Computational methodologies such as molecular mechanics (MM) and quantum mechanical (QM) methods play an important role in elucidating the detailed mechanisms of enzymatic reactions where experimental research measurements are not possible. Theories invoked by a variety of scientists indicate that enzymes work as structural scaffolds that serve to bring together and orient the reactants so that the reaction can proceed with minimum energy. Enzyme models can be utilized for mimicking enzyme catalysis and the development of novel prodrugs. Prodrugs are used to enhance the pharmacokinetics of drugs; classical prodrug approaches focus on alternating the physicochemical properties, while chemical modern approaches are based on the knowledge gained from the chemistry of enzyme models and correlations between experimental and calculated rate values of intramolecular processes (enzyme models). A large number of prodrugs have been designed and developed to improve the effectiveness and pharmacokinetics of commonly used drugs, such as anti-Parkinson (dopamine), antiviral (acyclovir), antimalarial (atovaquone), anticancer (azanucleosides), antifibrinolytic (tranexamic acid), antihyperlipidemia (statins), vasoconstrictors (phenylephrine), antihypertension (atenolol), antibacterial agents (amoxicillin, cephalexin, and cefuroxime axetil), paracetamol, and guaifenesin. This article describes the works done on enzyme models and the computational methods used to understand enzyme catalysis and to help in the development of efficient prodrugs.

scholarly journals Transition state theory can be used in studies of enzyme catalysis: lessons from simulations of tunnelling and dynamical effects in lipoxygenase and other systems

2006 ◽  
Vol 361 (1472) ◽  
pp. 1417-1432 ◽  
Author(s):  
Mats H.M Olsson ◽  
Janez Mavri ◽  
Arieh Warshel
Keyword(s):  
Transition State ◽  
Isotope Effect ◽  
Enzyme Catalysis ◽  
Potential Energy Surfaces ◽  
Transition State Theory ◽  
Enzymatic Reaction ◽  
Valence Bond ◽  
State Theory ◽  
Transmission Factor ◽  
Quantum Mechanical

The idea that enzyme catalysis involves special factors such as coherent fluctuations, quantum mechanical tunnelling and non-equilibrium solvation (NES) effects has gained popularity in recent years. It has also been suggested that transition state theory (TST) cannot be used in studies of enzyme catalysis. The present work uses reliable state of the art simulation approaches to examine the above ideas. We start by demonstrating that we are able to simulate any of the present catalytic proposals using the empirical valence bond (EVB) potential energy surfaces, the dispersed polaron model and the quantized classical path (QCP) approach, as well as the approximate vibronic method. These approaches do not treat the catalytic effects by phenomenological treatments and thus can be considered as first principles approaches (at least their ability to compare enzymatic reaction to the corresponding solution reactions). This work will consider the lipoxygenase reaction, and to lesser extent other enzymes, for specific demonstration. It will be pointed out that our study of the lipoxygenase reaction reproduces the very large observed isotope effect and the observed rate constant while obtaining no catalytic contribution from nuclear quantum mechanical (NQM) effects. Furthermore, it will be clarified that our studies established that the NQM effect decreases rather than increases when the donor–acceptor distance is compressed. The consequences of these findings in terms of the temperature dependence of the kinetic isotope effect and in terms of different catalytic proposals will be discussed. This paper will also consider briefly the dynamical effects and conclude that such effects do not contribute in a significant way to enzyme catalysis. Furthermore, it will be pointed out that, in contrast to recent suggestions, NES effects are not dynamical effects and should therefore be part of the activation free energy rather than the transmission factor. In view of findings of the present work and our earlier works, it seems that TST provides a quantitative tool for studies of enzyme catalysis and that the key open questions are related to the nature of the factors that lead to transition state stabilization.

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