Refined models of coordination between Al3+/Mg2+ and enzyme in molecular dynamics simulation in terms of ABEEM polarizable force field

Abstract

MF_X (AlF₃⁰, AlF₄^- and MgF₃^-) as transition state analogues of phosphoryl transfer enzymes (enzyme-MF_X-TSAs) is of great significance for study of the catalytic mechanism of phosphoryl transfer enzymes. Bonded model and non-bonded model based on the ABEEM polarizable force field (ABEEM PFF) are developed and applied to study the coordination of enzyme-MF_X-TSAs. The bond stretching of the bond containing metal is simulated by Morse potential energy function, because the change of chemical bond is described more accurately in a large range. The charge distribution of the system is distributed to multiple-charge-sites, including atomic site, σ bond site, π bond site and lone pair electron site. Partial charge can fluctuate according to the surrounding environment and molecular conformation. The reasonable charge distribution of 68 model molecules can be obtained, and the energy minimizations are performed in vacuum. Then, with the same parameters the charge distribution and the charge transfer of four complexes are obtained, and the energy minimization and molecular dynamics simulation in NVT ensemble are carried out in vacuum and explicit water solution. The results verify the correctness, rationality and transferability of the new parameters of ABEEM PFF, and the bonded model simulates more reasonable charge distribution and geometry. The parameters determined in this paper make up the blank of the parameters of MF_X and phosophoryl transfer enzymes containing Mg²⁺. The development of ABEEM PFF provides a refined tool for MF_X-TSAs to study the catalytic mechanism of phosphoryl transfer enzymes.

Keywords: ABEEM polarizable force field; Aluminum and magnesium fluoride; Charge distribution; Molecular dynamics simulation in explicit water solution; Phosphoryl transfer enzymes.