2013
DOI: 10.1021/ct400153r
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Toward an Automatic Determination of Enzymatic Reaction Mechanisms and Their Activation Free Energies

Abstract: We present a combination of the string method and a path collective variable for the exploration of the free energy surface associated to a chemical reaction in condensed environments. The on-the-fly string method is employed to find the minimum free energy paths on a multidimensional free energy surface defined in terms of interatomic distances, which is a convenient selection to study bond forming/breaking processes. Once the paths have been determined, a reaction coordinate is defined as a measure of the ad… Show more

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Cited by 45 publications
(76 citation statements)
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References 60 publications
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“…Unique in this approach was the construction of a single composite MD system containing 27 individual β2 molecules restrained to points on 3 × 3 × 3 grid inside a single large solvent box. Zinovjev et al used a combination of the on-the-fly string method and of path-collective variables (see Equations (28) and (29)) in a quantum-mechanics/molecular-mechanics approach to study a methyltransferase reaction [234].…”
Section: String Methods In Collective Variablesmentioning
confidence: 99%
“…Unique in this approach was the construction of a single composite MD system containing 27 individual β2 molecules restrained to points on 3 × 3 × 3 grid inside a single large solvent box. Zinovjev et al used a combination of the on-the-fly string method and of path-collective variables (see Equations (28) and (29)) in a quantum-mechanics/molecular-mechanics approach to study a methyltransferase reaction [234].…”
Section: String Methods In Collective Variablesmentioning
confidence: 99%
“…These computational levels have been shown to produce good results in the study of other methyltransferases. 44,55 These calculations were done with an interface between fDynamo and Gaussian09.…”
Section: Qm/mm Calculationsmentioning
confidence: 99%
“…This approach has already shown to be successful for the analysis of several complex enzymatic reactions. 44,55 In our calculations the coordinates used to trace the MFEP included all the interatomic distances associated with all possible bond breaking and forming events that could take place at each reaction step. Therefore no a priori assumptions have to be made about the reaction mechanism.…”
Section: Mhhai Reactivitymentioning
confidence: 99%
“…In the last decade, path‐based reaction coordinates (RCs) have become an important tool for free‐energy calculations in complex molecular systems . The idea of sampling the system along some relevant path in a multidimensional space of predefined descriptors (like Cartesian coordinates of essential atoms or, in general, any collective variables [CVs]) helps to overcome the so‐called “curse of dimensionality”: the exponential scaling of the computational cost versus the number of descriptors used.…”
Section: Introductionmentioning
confidence: 99%