Pharmacophore identification for matrix metalloproteinases by in silico investigations

Pharmacophores are a collection of universal chemical properties that characterizes the specific action of a ligand in the active site of a three-dimensional conformational model of a molecule. Aim. To define the pharmacophores, from some MMP-inhibitor complexes, defined experimentally in protein databank. Material and methods. We have used LiganScout software that supports the pharmacophore alignment and of important ligand molecules, based on their properties, in arbitrary combinations. The alignment of the two elements is realized by pairing only regardless the number of aligned elements. We have chosen 9 files crystalographically defined as MMP-inhibitor complexes: 1eub, 1fls, 1xuc, 1xud, 1xur, 1you, 1ztq, 456c and 830c, respectively. Results and discussions. Different type of inhibitors shows different pharmacophores, with respect to Zn coordination and for the hydrophobic tunnel in the enzyme binding pocket. Conclusions: it is important to understand substrate selectivity in order to develop new synthetic MMP inhibitors. Not only the Zn ion coordination in the P site is important but also the hydrophobicity of S1 tunnel can be a step in further computer design for potent inhibitor or enzyme modulation factors