Ab-initio dynamics of Gas-phase and Aqueous-phase Hydrolysis of
Adenosine Triphosphate
Abstract
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.