Accounting for the instantaneous disorder in the enzyme–substrate Michaelis complex to calculate the Gibbs free energy barrier of an enzyme reaction

Abstract

Many enzyme reactions present instantaneous disorder. These dynamic fluctuations in the enzyme-substrate Michaelis complexes generate a wide spread of energy barriers that cannot be experimentally observed, but that determines the...

Impacts of QM region sizes and conformation numbers on modelling enzyme reactions: a case study of polyethylene terephthalate hydrolase

“…According to the Eyring equation, this experimentally determined rate constant fluctuation corresponds to an energy barrier difference of about 6 kcal mol À1 . Several subsequent QM/MM MD simulations at both semi-empirical [47][48][49] and DFT levels 47,48,50 did consistently confirm this fluctuation. Notably, Neves et al evidenced that multi-PES DFT/MM calculations show similar results to DFT/MM MD simulations while less computing resources are needed.…”

Correlating Enzymatic Reactivity for Different Substrates using Transferable Data-Driven Collective Variables

“…Indeed, ML-based techniques are powerful tools when addressing multifaceted processes that encompass a large number of coupled degrees of freedom. For instance, in the case of enzyme catalysis, the substrate requires a precise arrangement in the active site to initiate a reaction, and thus, only a fraction of conformations within the enzyme:substrate complex ensemble are catalytically active [3][4][5][6][7][8][9][10][11][12][13][14][15] .…”