title: Virtual High-Throughput Screening for Matrix Metalloproteinase Inhibitors.
abstract: Structure-based virtual screening (SBVS) is a common method for the fast identification of hit structures at the beginning of a medicinal chemistry program in drug discovery. The SBVS, described in this manuscript, is focused on finding small molecule hits that can be further utilized as a starting point for the development of inhibitors of matrix metalloproteinase 13 (MMP-13) via structure-based molecular design. We intended to identify a set of structurally diverse hits, which occupy all subsites (S1'-S3', S2, and S3) centering the zinc containing binding site of MMP-13, by the virtual screening of a chemical library comprising more than ten million commercially available compounds. In total, 23 compounds were found as potential MMP-13 inhibitors using Glide docking followed by the analysis of the structural interaction fingerprints (SIFt) of the docked structures.
authors.affiliation: Department of Chemistry, The Scripps Research Institute, Jupiter, FL, 33458, USA. jchoi@scripps.edu.
authors.forename: Jun Yong
authors.initials: JY
authors.lastname: Choi
authors.affiliation: Department of Chemistry, The Scripps Research Institute, Jupiter, FL, 33458, USA.
authors.forename: Rita
authors.initials: R
authors.lastname: Fuerst
mesh_terms: D001665:Binding Sites; D019295:Computational Biology; D018360:Crystallography, X-Ray; D004353:Drug Evaluation, Preclinical; D057166:High-Throughput Screening Assays; D053509:Matrix Metalloproteinase 13 / Q000737:chemistry / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D062105:Molecular Docking Simulation / Q000379:methods*; D011487:Protein Conformation; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D054852:Small Molecule Libraries; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13
keywords: Docking; Matrix metalloproteinase; Structural interaction fingerprints; Structure-based virtual screening; Zn-chelating inhibitor