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Ab-initio dynamics of Gas-phase and Aqueous-phase Hydrolysis of Adenosine Triphosphate
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  • Raghav Saxena,
  • Phani Kumar Avanigadda,
  • Raghvendra Singh,
  • Vishal Agarwal
Raghav Saxena
Indian Institute of Technology Kanpur
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Phani Kumar Avanigadda
Indian Institute of Technology Kanpur
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Raghvendra Singh
Indian Institute of Technology Kanpur
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Vishal Agarwal
Indian Institute of Technology Kanpur
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Adenosine triphosphate (ATP) hydrolysis is a well-known biological reaction which plays an important role in many biological processes. In this study, we have modelled the non-enzymatic hydrolysis of ATP in the gas-phase and the aqueous-phase by performing ab initio molecular dynamics simulations combined with an enhanced sampling technique. In the gas-phase, we studied hydrolysis of fully protonated ATP molecule and in the aqueous-phase, we studied hydrolysis of ATP coordinated with: a) two H+ ions (H-ATP), b) Mg2+ (Mg-ATP) and c) Ca2+ (Ca-ATP). We show that gas-phase ATP hydrolysis follows a two-step dissociative mechanism via a highly stable metaphosphate intermediate. The Adenine group of the ATP molecule plays a crucial role of a general base; temporarily accepting protons and, thus helping in the elimination-addition process. In the aqueous-phase hydrolysis of ATP, we find that the cage of solvent molecules increases the stability of the terminal phospho-anhydride bond through a well-known cage-effect. Further, we find that the aqueous-phase hydrolysis happens with the help of nearby water molecules, which assumes the role of a base assisting in proton diffusion through Grotthuss mechanism. We obtained much lower free-energy barriers for the aqueous-phase hydrolysis of ATP coordinated with divalent ions (Mg2+ and Ca2+) compared to hydrolysis of ATP coordinated with only H+ ions, suggesting a clear catalytic effect of the divalent ions. We find a single-step dissociative-type mechanism for Mg-ATP, while we find a SN-2-type concerted hydrolysis pathway for Ca-ATP.

Peer review status:Published

26 Oct 2020Submitted to International Journal of Quantum Chemistry
02 Nov 2020Submission Checks Completed
02 Nov 2020Assigned to Editor
05 Nov 2020Reviewer(s) Assigned
05 Nov 2020Review(s) Completed, Editorial Evaluation Pending
05 Nov 2020Editorial Decision: Revise Minor
10 Nov 20201st Revision Received
13 Nov 2020Assigned to Editor
13 Nov 2020Submission Checks Completed
13 Nov 2020Reviewer(s) Assigned
07 Dec 2020Review(s) Completed, Editorial Evaluation Pending
07 Dec 2020Editorial Decision: Revise Major
30 Dec 20202nd Revision Received
04 Jan 2021Submission Checks Completed
04 Jan 2021Assigned to Editor
04 Jan 2021Reviewer(s) Assigned
16 Jan 2021Review(s) Completed, Editorial Evaluation Pending
18 Jan 2021Editorial Decision: Accept
25 Feb 2021Published in International Journal of Quantum Chemistry. 10.1002/qua.26615