Molecular dynamics simulation on complex of HPPK and substrate HP

6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) catalyzes the transfer of pyrophosphoryl from adenosine triphosphate (ATP) to 6-hydroxymethyl-7, 8-dihydropterin (HP), which is important in the folate pathway. So HPPK is thought to be an ideal target for developing novel antimicrobial agents. In the present paper, HP and ATP were docked into HPPK with two Mg2+ ions and three water molecules, using the flexible dock program (FlexiDock). A 2000 ps molecular dynamics simulation was carried out to refine the docked complex system. The simulation shows the stability and validity of the complex structure. Two Mg2+ ions are both octahedral coordination. One Mg2+ ion is chelated with an oxygen atom of HP, which is favorable to the transfer of pyrophosphoryl from ATP to HP. The complex structure derived from MD is more stable and rational than the docked complex. Our simulation result and the predicted complex structure would be useful in designing antimicrobial inhibitor.