Search results for "transition state theory"
showing 10 items of 14 documents
Quantifying the limits of transition state theory in enzymatic catalysis
2017
Significance Transition state theory (TST) is the most popular theory to calculate the rates of enzymatic reactions. However, in some cases TST could fail due to the violation of the nonrecrossing hypothesis at the transition state. In the present work we show that even for one of the most controversial enzymatic reactions—the hydride transfer catalyzed by dihydrofolate reductase—the error associated to TST represents only a minor correction to the reaction rate. Moreover, this error is actually larger for the reaction in solution than in the enzymatic active site. Based on this finding and on previous studies we propose an “enzymatic shielding” hypothesis which encompasses various aspects …
Heavy enzymes—experimental and computational insights in enzyme dynamics
2014
The role of protein motions in the chemical step of enzyme-catalyzed reactions is the subject of an open debate in the scientific literature. The systematic use of isotopically substituted enzymes has been revealed as a useful tool to quantify the role of these motions. According to the Born-Oppenheimer approximation, changing the mass of the protein does not change the forces acting on the system but alters the frequencies of the protein motions, which in turn can affect the rate constant. Experimental and theoretical studies carried out in this field are presented in this article and discussed in the framework of Transition State Theory.
A theory ofnonverticaltriplet energy transfer in terms of accurate potential energy surfaces: The transfer reaction from π,π* triplet donors to 1,3,5…
2004
Triplet energy transfer (TET) from aromatic donors to 1,3,5,7-cyclooctatetraene (COT) is an extreme case of "nonvertical" behavior, where the transfer rate for low-energy donors is considerably faster than that predicted for a thermally activated (Arrhenius) process. To explain the anomalous TET of COT and other molecules, a new theoretical model based on transition state theory for nonadiabatic processes is proposed here, which makes use of the adiabatic potential energy surfaces (PES) of reactants and products, as computed from high-level quantum mechanical methods, and a nonadiabatic transfer rate constant. It is shown that the rate of transfer depends on a geometrical distortion paramet…
Transition state ensemble optimization for reactions of arbitrary complexity.
2015
In the present work, we use Variational Transition State Theory (VTST) to develop a practical method for transition state ensemble optimization by looking for an optimal hyperplanar dividing surface in a space of meaningful trial collective variables. These might be interatomic distances, angles, electrostatic potentials, etc. Restrained molecular dynamics simulations are used to obtain on-the-fly estimates of ensemble averages that guide the variations of the hyperplane maximizing the transmission coefficient. A central result of our work is an expression that quantitatively estimates the importance of the coordinates used for the localization of the transition state ensemble. Starting fro…
Exploring Chemical Reactivity in Enzyme Catalyzed Processes Using QM/MM Methods: An Application to Dihydrofolate Reductase
2015
Enzymes are the catalysts used by living organisms to accelerate chemical processes under physiological conditions. In this chapter, we illustrate the current view about the origin of their extraordinary rate enhancement based on molecular simulations and, in particular, on methods based on the combination of Quantum Mechanics and Molecular Mechanics potentials which provide a solution to treat the chemical reactivity of these large and complex molecular systems. Computational studies on Dihydrofolate Reductase have been selected as a conductor wire to present the evolution and difficulties to model chemical reactivity in enzymes. The results discussed here show that experimental observatio…
A simple model for barrier frequencies for enzymatic reactions.
2010
We present a simple model to rationalize the effects of environment on the reaction barrier frequencies derived from free energy profiles. These frequencies are relevant in deviations of a rate constant from its transition state theory value and in determining which environmental dynamics participate in the reaction. In particular, this simple model can be used to understand the changes in the reaction barrier frequencies of an enzymatic catalyzed reaction and the corresponding uncatalyzed process in aqueous solution, a change which has implications for dynamical environmental effects on the enzymatic reaction. Two possible cases are analyzed, in which the polarity (charge separation/locali…
Origin of Enzymatic Kinetic Isotope Effects in Human Purine Nucleoside Phosphorylase
2017
Here we report a study of the effect of heavy isotope labeling on the reaction catalyzed by human purine nucleoside phosphorylase (hPNP) to elucidate the origin of its catalytic effect and of the enzymatic kinetic isotope effect (EKIE). Using quantum mechanical and molecular mechanical (QM/MM) molecular dynamics (MD) simulations, we study the mechanism of the hPNP enzyme and the dynamic effects by means of the calculation of the recrossing transmission coefficient. A free energy surface (FES), as a function of both a chemical and an environmental coordinate, is obtained to show the role of the environment on the chemical reaction. Analysis of reactive and nonreactive trajectories allows us …
Fission fragment angular distributions in the capture reactions 50Ti, 56Fe + 208Pb
2008
The analysis of %-ray mult ip l ic i t ies measured I in coincidence with capture fission events in reactions of 26Mg through 54Cr, 58Fe, and 64Ni with 208pb in terms of Ko and~eff revealed1 that the resulting values of ~ /~e f f were rather independent of for a given system and, in a compound nucleus picture, were more in agreement with the 'shape of the non-rotating saddle than with the actually expected rotating saddle I f non-compound systenmhave to be considered these values of ~/J~ff__ shapes. suggested at least that the captured systems near the turning point from the inward radial motion to symmetric fragmentation had reached a remarkable compactness.
Application of SQMFF Vibrational Calculations to Transition States: DFT and ab Initio Study of the Kinetics of Methyl Azide and Ethyl Azide Thermoly…
1998
DFT including nonlocal corrections and ab initio calculations at MP2 and MP4 levels of theory have been performed in order to provide information concerning the mechanism of the rate limiting step of the thermal decomposition of methyl azide and ethyl azide. The chemically interesting points of the ground-state potential energy surface have been fully optimized, and a detailed normal-mode analysis for the reagents and the transition states is presented. The well-established scaled quantum mechanical force field method has been used to obtain reliable vibrational frequencies for these molecular structures. The force fields of transition states have been modified by using the scale factors co…
Transition state theory thermal rate constants and RRKM-based branching ratios for the N((2)D) + CH(4) reaction based on multi-state and multi-refere…
2012
International audience; Multireference single and double configuration interaction (MRCI) calculations including Davidson (+Q) or Pople (+P) corrections have been conducted in this work for the reactants, products, and extrema of the doublet ground state potential energy surface involved in the N(2D) + CH4 reaction. Such highly correlated ab initio calculations are then compared with previous PMP4, CCSD(T), W1, and DFT/B3LYP studies. Large relative differences are observed in particular for the transition state in the entrance channel resolving the disagreement between previous ab initio calculations. We confirm the existence of a small but positive potential barrier (3.86 +/- 0.84 kJ mol-1…