Virtual Screening of Lead Chemicals Based on HPX Domain of MT1-MMP

Receptor structured-based virtual screening is routinely used in computer aided drug design. Membrane-type matrix metalloproteinase-l (MTl-MMP, also called MMP-14) plays a key role in tumor invasion and metastasis by degrading the extracellular matrix and activating proMMP2. The Hemopexin-like (HPX) domain of MT1-MMP is required for MTl-MMP-mediated tumor invasion and growth in three-dimension type I collagen matrix. Here, we describe the virtual screening of lead chemicals based on the HPX domain of MT1-MMP. DOCK, MVD and metaPocket were used in detecting and identifying of the potential active sites on the surface of HPX domain of MT1-MMP. DOCK and AutoDock were used for docking ligands from Specs chemical database to two potential active sites. The result indicates that the sphere cluster 3 identified by the program in DOCK, sphgen, might be a right active site used for HPX structured-based docking study. A group of chemical compounds have been identified and may be used for further study as lead molecules. Our study also provides better insight to virtual screening study based on receptor in condition of no receptor-ligand complex crystal structure is available.