Abstract

PM3 based calculations of interaction energy between metalloproteinases and hydroxamate inhibitors

Author(s): R.K.Singh, Surabhi Rai, P.P.Singh

Metalloproteinases (MMP) are zinc-containing enzymes; that mediate the break down of connective tissue. The therapeutic inhibitors are chelating agents such as hydroxamates (RNHOH). The interaction between enzyme and the inhibitor is two fold. The nitrogen of RNHOH chelates with zinc, whereas the R substituent has polar interaction with histidine part of the enzyme. The chelating ability of the RNHOH has been studiedwith the help of transfer of charge N and and lowering of energy E on interaction of RNHOH with Zn++. The magnitude of interaction has been evaluated by equation ÄN = (÷o A- ÷o B) / 2(çA+ çB) and ÄE = -(÷o A- ÷o B) 2 / 4(çA+ çB). Based on DFT principles the interaction energy Eint between Zn++ of MMP and nitrogen of RNHOH has also been calculated by using the values of softness, chemical potential and number of electrons. The results of N, E and Eint have been compared. The interaction between R of RNHOH and histidine of the enzymes has been studied by identifying the sites of hydrogen bonding between hydrogen of histidine and sulphonyl, ester and carbonyl oxygen of inhibitors and vice versa. The study provides new descriptors, N, E, Eint for application in biological system.