Taking Ockham's razor to enzyme dynamics and catalysis

Glowacki, David R.; Harvey, Jeremy N.; Mulholland, Adrian J.

doi:10.1038/nchem.1244

Cited by 236 publications

(278 citation statements)

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“…Several of these proposals suggest that the anomalous temperature and pressure dependences of experimentally observed reaction rates and kinetic isotope effects are the consequence of protein motions on the pico-to femtosecond timescale that reduce the width and/ or height of the potential energy barrier along the chemical reaction coordinate. However, a connection between promoting motions and potential energy barrier modulation has never been demonstrated directly, and recent work has shown that the temperature dependence of kinetic isotope effects can be accounted for by conformational effects for a number of enzymes (5). Whereas some authors postulate dynamics as a key driving force in catalysis (1)(2)(3)(4), others have performed analyses showing activation free-energy reduction, which is an equilibrium property, to be the source of catalysis (6)(7)(8)(9)(10)(11)(12)(13)(14).…”

mentioning

confidence: 99%

Unraveling the role of protein dynamics in dihydrofolate reductase catalysis

Luk

Ruiz‐Pernía

Dawson

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Protein dynamics have controversially been proposed to be at the heart of enzyme catalysis, but identification and analysis of dynamical effects in enzyme-catalyzed reactions have proved very challenging. Here, we tackle this question by comparing an enzyme with its heavy ( 15 N, 13 C, 2 H substituted) counterpart, providing a subtle probe of dynamics. The crucial hydride transfer step of the reaction (the chemical step) occurs more slowly in the heavy enzyme. A combination of experimental results, quantum mechanics/molecular mechanics simulations, and theoretical analyses identify the origins of the observed differences in reactivity. The generally slightly slower reaction in the heavy enzyme reflects differences in environmental coupling to the hydride transfer step. Importantly, the barrier and contribution of quantum tunneling are not affected, indicating no significant role for "promoting motions" in driving tunneling or modulating the barrier. The chemical step is slower in the heavy enzyme because protein motions coupled to the reaction coordinate are slower. The fact that the heavy enzyme is only slightly less active than its light counterpart shows that protein dynamics have a small, but measurable, effect on the chemical reaction rate.kinetics | computational chemistry | biological chemistry | biophysics | quantum biology

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confidence: 99%

Unraveling the role of protein dynamics in dihydrofolate reductase catalysis

Luk

Ruiz‐Pernía

Dawson

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

127

262

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“…In conclusion, while we agree that it is reasonable to use Ockham's razor to exclude the dynamical proposal, 183 however, we also believe that basically using the "inductive" approach of showing that the proposal does not work for any current test case (as we have done here) is the best way to establish that enzyme catalysis is not due to dynamical effects.…”

Section: Discussionmentioning

confidence: 95%

Enhancement of the droplet nucleation in a dense supersaturated Lennard-Jones vapor

Zhukhovitskii

2016

The Journal of Chemical Physics

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The vapor–liquid nucleation in a dense Lennard-Jones system is studied analytically and numerically. A solution of the nucleation kinetic equations, which includes the elementary processes of condensation/evaporation involving the lightest clusters, is obtained, and the nucleation rate is calculated. Based on the equation of state for the cluster vapor, the pre-exponential factor is obtained. The latter diverges as a spinodal is reached, which results in the nucleation enhancement. The work of critical cluster formation is calculated using the previously developed two-parameter model (TPM) of small clusters. A simple expression for the nucleation rate is deduced and it is shown that the work of cluster formation is reduced for a dense vapor. This results in the nucleation enhancement as well. To verify the TPM, a simulation is performed that mimics a steady-state nucleation experiments in the thermal diffusion cloud chamber. The nucleating vapor with and without a carrier gas is simulated using two different thermostats for the monomers and clusters. The TPM proves to match the simulation results of this work and of other studies.

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“…The manner in which it is plotted suggests analogy with the concept of an energy landscape, which has become a fundamental idea guiding how chemists and physicists think about both kinetics and dynamics in a range of chemical systems, from small molecules to complex materials and biochemical systems. 52,53 An energy landscape is effectively a topological map of a system's potential energy, V, at a range of different congurations. Within any localized region of the energy landscape, the gradient of the energy, dV/dq, relates the topology of the energy landscape to the classical forces felt by a particular molecular conguration.…”

Section: Depth Images and Energy Landscapesmentioning

confidence: 99%

A GPU-accelerated immersive audio-visual framework for interaction with molecular dynamics using consumer depth sensors

et al. 2014

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A GPU-accelerated immersive audiovisual framework for interaction with molecular dynamics using consumer depth sensors. Faraday Discussions, 169. pp. 63-87. ISSN 1359-6640 Available from: http://eprints.uwe.ac.uk/23115We recommend you cite the published version. The publisher's URL is: http://dx.doi.org/10.1039/C4FD00008K Refereed: Yes First published online 19 Mar 2014Disclaimer UWE has obtained warranties from all depositors as to their title in the material deposited and as to their right to deposit such material. UWE makes no representation or warranties of commercial utility, title, or fitness for a particular purpose or any other warranty, express or implied in respect of any material deposited. UWE makes no representation that the use of the materials will not infringe any patent, copyright, trademark or other property or proprietary rights.UWE accepts no liability for any infringement of intellectual property rights in any material deposited but will remove such material from public view pending investigation in the event of an allegation of any such infringement. PLEASE SCROLL DOWN FOR TEXT.A GPU-accelerated immersive audio-visual framework for interaction with molecular dynamics using consumer depth sensors † With advances in computational power, the rapidly growing role of computational/ simulation methodologies in the physical sciences, and the development of new human-computer interaction technologies, the field of interactive molecular dynamics seems destined to expand. In this paper, we describe and benchmark the software algorithms and hardware setup for carrying out interactive molecular dynamics utilizing an array of consumer depth sensors. The system works by interpreting the human form as an energy landscape, and superimposing this landscape on a molecular dynamics simulation to chaperone the motion of the simulated atoms, affecting both graphics and sonified simulation data. GPU acceleration has been key to achieving our target of 60 frames per second (FPS), giving an extremely fluid interactive experience. GPU acceleration has also allowed us to scale the system for use in immersive 360 spaces with an array of up to ten depth sensors, allowing several users to simultaneously chaperone the dynamics. The flexibility of our platform for carrying out molecular dynamics simulations has been considerably enhanced by wrappers that facilitate fast communication with a portable selection of GPU-accelerated molecular force evaluation routines. In this paper, we describe a 360 atmospheric molecular dynamics simulation we have run in a chemistry/physics education context. We also describe initial tests in which users have been able to chaperone the dynamics of 10-alanine peptide embedded in an explicit water solvent. Using this system, both expert and novice users have been able to accelerate peptide rare event dynamics by 3-4 orders of magnitude.

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Taking Ockham's razor to enzyme dynamics and catalysis

Cited by 236 publications

References 80 publications

Unraveling the role of protein dynamics in dihydrofolate reductase catalysis

Unraveling the role of protein dynamics in dihydrofolate reductase catalysis

Enhancement of the droplet nucleation in a dense supersaturated Lennard-Jones vapor

A GPU-accelerated immersive audio-visual framework for interaction with molecular dynamics using consumer depth sensors

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