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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.

SUBMITTER: Choi JY

PROVIDER: S-EPMC6485679 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Virtual High-Throughput Screening for Matrix Metalloproteinase Inhibitors.

Choi Jun Yong JY Fuerst Rita R

Methods in molecular biology (Clifton, N.J.) 20170101

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 subsi ...[more]

PMID: 28299742

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