The IMPDH (Inosine monophosphate dehydrogenase)-II is largely produced in cancer cells. Extensive MD-simulation (2 ns) of the 1B3O, 1NFB, 1NF7, 1LRT, and 1MEW PDB-structures revealed the presence of a conserved water molecule, which is H-bonded and stabilized by the surrounding ribose hydroxyl (O2) of inhibitor, nitrogen (NN) of cofactor, carboxyl oxygen (OD2) and amide nitrogen atoms of the active site Asp 364 and Asn 303 of human. These water-mediated interaction are partially supported in the solvated and X-ray structures. The stereochemistry of the four- centered H-bonds around the conserved water center may be exploited to design a better model inhibitor for IMPDH-II.

Key words: IMPDH II, Molecular Dynamics, Inhibitor.