Abstract
Hydrolysis reaction of nucleotide triphosphate, ATP and GTP in particular, has been widely found as regulatory machinery for protein functional expression in the cell. Nonetheless, the microscopic mechanisms for functional regulations via the chemical reactions are mostly elusive so far, due to technical difficulty of both experimental observations and conventional theoretical simulations. We addressed the problem by examining the conjecture that Coulomb repulsion interaction between products, ADP/GDP and inorganic phosphate (Pi), execute the mechanical works upon the system. GTP hydrolysis reaction for Ras-GTP-GAP system was effectively simulated in the framework of classical atomistic molecular dynamic simulations by switching force field parameters between the reactant and product systems. We observed transient increase of kinetic energy of GDP and Pi, and the neighboring functional domains of Ras. One of such functional regions, P-loop, shows increase of nonbonded potential energy, which is retained even after gained kinetic energy is dissipated. This change is explained from rearrangement of hydrogen bonding between P-loop and GDP. Interestingly, even if increase of kinetic energy is suppressed, the above change is reproduced through GTP-GDP conversion. This observation suggests that conversion of chemical species itself plays essential roles in regulation rather than transient heat generation via the hydrolysis reactions.
Competing Interest Statement
The authors have declared no competing interest.