Ab initio dynamics of gas‐phase and aqueous‐phase hydrolysis of adenosine triphosphate

Abstract

AbstractIn 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. The nature of the ions has an important effect on the mechanism of the reaction. We find a two‐step dissociative‐type mechanism for H‐ATP, a single‐step dissociative‐type mechanism for Mg‐ATP, and an SN‐2 type concerted hydrolysis pathway for Ca‐ATP.