6533b7d2fe1ef96bd125f649
RESEARCH PRODUCT
Quantifying the limits of transition state theory in enzymatic catalysis
Iñaki TuñónKirill Zinovjevsubject
Surface (mathematics)enzymatic catalysisDegrees of freedom (statistics)Molecular Dynamics Simulation010402 general chemistry01 natural sciencesEnzyme catalysisReaction coordinateReaction rateTransition state theoryMolecular dynamicsdihydrofolate reductasetransmission coefficientComputational chemistry0103 physical sciencesHumansdynamic effectsStatistical physicsIonsMultidisciplinary010304 chemical physicsChemistryState (functional analysis)Biological Sciencesbacterial infections and mycoses0104 chemical sciencesChemistryBiophysics and Computational BiologyKineticsTetrahydrofolate Dehydrogenasetransition state theoryPhysical SciencesBiocatalysisdescription
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 of the catalytic process.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2017-11-01 | Proceedings of the National Academy of Sciences |