Transition Path Sampling Based Calculations of Free Energies for Enzymatic Reactions: The Case of Human Methionine Adenosyl Transferase and Plasmodium vivax Adenosine Deaminase.

ABSTRACT: Transition path sampling (TPS) is widely used for the calculations of reaction rates, transition state structures, and reaction coordinates of condensed phase systems. Here we discuss a scheme for the calculation of free energies using the ensemble of TPS reactive trajectories in combination with a window-based sampling technique for enzyme-catalyzed reactions. We calculate the free energy profiles of the reactions catalyzed by the human methionine S-adenosyltransferase (MAT2A) enzyme and the Plasmodium vivax adenosine deaminase (pvADA) enzyme to assess the accuracy of this method. MAT2A catalyzes the formation of S-adenosine-l-methionine following a S_N2 mechanism, and using our method, we estimate the free energy barrier for this reaction to be 16 kc

SUBMITTER: Balasubramani SG 

PROVIDER: S-EPMC9444332 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature