Drastic Compensation of Electronic and Solvation Effects on ATP Hydrolysis Revealed through Large-Scale QM/MM Simulations Combined with a Theory of Solutions

Hideaki Takahashi, Satoru Umino, Yuji Miki, Ryosuke Ishizuka, Shu Maeda, Akihiro Morita, Makoto Suzuki, Nobuyuki Matubayasi

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Hydrolysis of adenosine triphosphate (ATP) is the "energy source" for a variety of biochemical processes. In the present work, we address key features of ATP hydrolysis: the relatively moderate value (about -10 kcal/mol) of the standard free energy, ΔGhyd, of reaction and the insensitivity of ΔGhyd to the number of excess electrons on ATP. We conducted quantum mechanical/molecular mechanical simulation combined with the energy-representation theory of solutions to analyze the electronic-state and solvation contributions to ΔGhyd. It was revealed that the electronic-state contribution in ΔGhyd is largely negative (favorable) upon hydrolysis, due to the reduction of electrostatic repulsion accompanying the breakage of the P-O bond. In contrast, the solvation effect was found to be strongly more favorable on the reactant side. Thus, we showed that a drastic compensation of the two opposite effects takes place, leading to the modest value of ΔGhyd at each number of excess electrons examined. The computational analyses were also conducted for pyrophosphate ions (PPi), and the parallelism between the ATP and PPi hydrolyses was confirmed. Classical molecular dynamics simulation was further carried out to discuss the effect of the solvent environment; the insensitivity of ΔGhyd to the number of excess electrons was seen to hold in solvent water and ethanol. (Graph Presented).

Original languageEnglish
Pages (from-to)2279-2287
Number of pages9
JournalJournal of Physical Chemistry B
Volume121
Issue number10
DOIs
Publication statusPublished - 2017 Mar 16

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Surfaces, Coatings and Films
  • Materials Chemistry

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