title: A Cross-Docking Study on Matrix Metalloproteinase Family.
abstract: BACKGROUND
  Matrix metalloproteinases (MMPs) contribute to various physiological and pathophysiological processes. An imbalance in MMP activity causes pathological conditions including inflammatory diseases, cancer, and cardiovascular diseases. Each MMP member has many 3D structures available; therefore, selecting one structure for virtual screening becomes challenging.
  
  
  METHODS
  In this study, we used the cross-docking approach to rank the available MMP structures for their probable successful performance in virtual screening. To determine structures that would offer best average RMSD (root mean square deviation), we performed cross-docking studies on 123 holo (protein-ligand) structures of seven MMP enzyme groups (MMP-1, MMP-3, MMP-7, MMP-8, MMP-9, MMP-12, and MMP-13).
  
  
  RESULTS
  MMP enzymes with more flexible residues had fewer structures with RMSD < 2.0 A. Further, same resolution and binding affinities, difference in ligand size, and chemotype of the co-crystalized ligand were parameters that could greatly affect the corresponding cross-dock results and the calculated average RMSD for the structures. Four of the six best MMP-12 receptors, which were identified using the average RMSD metric, had the highest EF1% (emrichment factor) in the retrospective enrichment study.
  
  
  CONCLUSIONS
  According to the enrichment results, structures with lower average RMSD have a high probability of being appropriate candidates. These study findings will help in receptor selection for an MMP virtual screening protocol and lead to better enrichment of MMP inhibitors.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Ramezani
authors.affiliation: Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. shamsaraj@mums.ac.ir.
authors.forename: Jamal
authors.initials: J
authors.lastname: Shamsara
mesh_terms: D008024:Ligands; D020782:Matrix Metalloproteinases / Q000737:chemistry* / Q000378:metabolism*; D062105:Molecular Docking Simulation; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D008024:Ligands; D020782:Matrix Metalloproteinases