Isomerization dynamics in liquids by molecular dynamics

Rosenberg, Robert; Berne, B. J.; Chandler, David

doi:10.1016/0009-2614(80)80487-8

Cited by 160 publications

(93 citation statements)

References 14 publications

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“…50 Another way is to use the "reactive flux" method. [52][53][54] An additional way is offered by evaluating the average velocity by which productive trajectories pass the TS. This average velocity can be obtained from the autocorrelation of the EVB energy gap.…”

Section: Enzyme Catalysis and The Transmission Coefficientmentioning

confidence: 99%

Perspective: Defining and quantifying the role of dynamics in enzyme catalysis

Warshel

Bora

2016

The Journal of Chemical Physics

190

168

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Enzymes control chemical reactions that are key to life processes, and allow them to take place on the time scale needed for synchronization between the relevant reaction cycles. In addition to general interest in their biological roles, these proteins present a fundamental scientific puzzle, since the origin of their tremendous catalytic power is still unclear. While many different hypotheses have been put forward to rationalize this, one of the proposals that has become particularly popular in recent years is the idea that dynamical effects contribute to catalysis. Here, we present a critical review of the dynamical idea, considering all reasonable definitions of what does and does not qualify as a dynamical effect. We demonstrate that no dynamical effect (according to these definitions) has ever been experimentally shown to contribute to catalysis. Furthermore, the existence of non-negligible dynamical contributions to catalysis is not supported by consistent theoretical studies. Our review is aimed, in part, at readers with a background in chemical physics and biophysics, and illustrates that despite a substantial body of experimental effort, there has not yet been any study that consistently established a connection between an enzyme’s conformational dynamics and a significant increase in the catalytic contribution of the chemical step. We also make the point that the dynamical proposal is not a semantic issue but a well-defined scientific hypothesis with well-defined conclusions.

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Section: Enzyme Catalysis and The Transmission Coefficientmentioning

confidence: 99%

Perspective: Defining and quantifying the role of dynamics in enzyme catalysis

Warshel

Bora

2016

The Journal of Chemical Physics

190

168

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“…This type of isomerization has served as a basic model for modern chemical reaction kinetic theory and molecular dynamics simulation studies in condensed phases. [105][106][107][108][109] In spite of extensive theoretical investigation, until recently 110 no corresponding kinetic experiments have been performed to test the results, partially due to the low rotational energy barrier of the n-butane (B3.4 kcal mol À1 ) and other simple 1,2-disubstituted ethane derivatives. 111 Theoretical studies show that the isomerization time scale (1/k, k is the rate constant) is 10-100 ps at room temperature in liquids.…”

Section: B the Influence Of Substrate Binding Of Enzyme Dynamicsmentioning

confidence: 99%

“…111 Theoretical studies show that the isomerization time scale (1/k, k is the rate constant) is 10-100 ps at room temperature in liquids. [105][106][107][108][109]112 The room temperature time scale is much shorter than the microsecond and longer time scale measurements that can be made with dynamic nuclear magnetic resonance spectroscopy, a widely used method for studying slow temperature dependent isomerization kinetics at low temperatures for compounds with high barriers. 113 Other methods to study fast isomerization dynamics under thermal equilibrium such as linear IR and Raman line shape analysis, 114,115 are hampered by the contributions from multiple factors in addition to isomerization.…”

Section: B the Influence Of Substrate Binding Of Enzyme Dynamicsmentioning

confidence: 99%

Probing dynamics of complex molecular systems with ultrafast 2D IR vibrational echo spectroscopy

Finkelstein

Zheng

Ishikawa

et al. 2007

Phys. Chem. Chem. Phys.

148

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Ultrafast 2D IR vibrational echo spectroscopy is described and a number of experimental examples are given. Details of the experimental method including the pulse sequence, heterodyne detection, and determination of the absorptive component of the 2D spectrum are outlined. As an initial example, the 2D spectrum of the stretching mode of CO bound to the protein myoglobin (MbCO) is presented. The time dependence of the 2D spectrum of MbCO, which is caused by protein structural evolution, is presented and its relationship to the frequency-frequency correlation function is described and used to make protein structural assignments based on comparisons to molecular dynamics simulations. The 2D vibrational echo experiments on the protein horseradish peroxidase are presented. The time dependence of the 2D spectra of the enzyme in the free form and with a substrate bound at the active site are compared and used to examine the influence of substrate binding on the protein's structural dynamics. The application of 2D vibrational echo spectroscopy to the study of chemical exchange under thermal equilibrium conditions is described. 2D vibrational echo chemical exchange spectroscopy is applied to the study of formation and dissociation of organic solute-solvent complexes and to the isomerization around a carbon-carbon single bond of an ethane derivative.

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“…Processes of this kind include side-chain rotational isomerization (1-5), motion of small ligand molecules through steric bottlenecks within a protein (6, 7), and covalent bond rearrangements in enzymes (8,9). In these cases, the important energy changes during the transition are associated with displacements of atoms within a local region (4,5,7,10), while the remainder ofthe protein plays a role analogous to a solvent or a solid matrix in other condensedphase reactions (11)(12)(13)(14).An important goal in the theoretical study ofprotein dynamics is the characterization of such activated processes (15,16). This includes the calculation ofexperimentally accessible quantities, like rate constants and activation energies, and the determination of the space and time correlations of the atomic motions involved in the transitions.…”

mentioning

confidence: 99%

Dynamical theory of activated processes in globular proteins.

Northrup¹,

Pear²,

Lee³

et al. 1982

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

195

139

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A method is described for calculating the reaction rate in globular proteins ofactivated processes such as ligand binding or enzymatic catalysis. The method is based on the determination of the probability that the system is in the transition state and of the magnitude of the reactive flux for transition-state systems. An "umbrella sampling" simulation procedure is outlined for evaluating the transition-state probability. The reactive flux is obtained from an approach described previously for calculating the dynamics of transition-state trajectories. An application to the rotational isomerization of an aromatic ring in the bovine pancreatic trypsin inhibitor is presented. The results demonstrate the feasibility ofcalculating rate constants for reactions in proteins and point to the importance of solvent effects for reactions that occur near the protein surface.Many of the biological functions of globular proteins involve activated processes in which the motion from one stable or intermediate state to another is limited by the rate of activation to a transition state of relatively high energy. Processes of this kind include side-chain rotational isomerization (1-5), motion of small ligand molecules through steric bottlenecks within a protein (6, 7), and covalent bond rearrangements in enzymes (8,9). In these cases, the important energy changes during the transition are associated with displacements of atoms within a local region (4,5,7,10), while the remainder ofthe protein plays a role analogous to a solvent or a solid matrix in other condensedphase reactions (11)(12)(13)(14).An important goal in the theoretical study ofprotein dynamics is the characterization of such activated processes (15,16). This includes the calculation ofexperimentally accessible quantities, like rate constants and activation energies, and the determination of the space and time correlations of the atomic motions involved in the transitions. Some progress toward this goal has been achieved in studies of the rotation of the rings of aromatic side chains in globular proteins (4, 5, 10) for which NMR data are available (1-3).In the initial investigations, empirical energy functions ofthe molecular mechanics type were used to estimate the effective energy barriers for ring rotation in the pancreatic trypsin inhibitor (4,5,17). In these calculations, each ring was held fixed in several orientations while the remainder of the protein was allowed to relax somewhat by partial energy minimization. The residual barriers, which are much smaller than those calculated with a rigid protein matrix, are in general agreement with the experimental activation enthalpies. These studies showed that the observed barriers are primarily due to repulsive nonbonded interactions between the rings and neighboring atoms and that matrix relaxation plays an essential role in allowing the rotations to occur at observable rates. However, the static character of this approach does not allow study of the dynamical details of the transitions nor of the entropic con...

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Isomerization dynamics in liquids by molecular dynamics

Cited by 160 publications

References 14 publications

Perspective: Defining and quantifying the role of dynamics in enzyme catalysis

Perspective: Defining and quantifying the role of dynamics in enzyme catalysis

Probing dynamics of complex molecular systems with ultrafast 2D IR vibrational echo spectroscopy

Dynamical theory of activated processes in globular proteins.

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