6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) catalyzes pyrophosphoryl transfer from adenosine triphosphate (ATP) to 6-hydroxymethyl-7,8-dihydropterin (HP), the first reaction in the folate pathway, and is thought to be an ideal target for developing novel antimicrobial agents. In the present work, molecular docking studies on the interactions of HPPK with the substrate analogues have been performed. Particularly, the effect of the intrinsic metal ion upon the docking has been examined. It has been showed that the incorporation of Mg^2＋cation in the molecular docking processes plays an important role not only in obtaining reliable docking results but also in improving the hit ratio in the "in silico" drug screening. This may provide some helpful information for our designing new antimicrobial agents based on HPPK.

Key words: 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK), molecular dynamics, docking, metal ion effect