Matrix metalloproteinase target family landscape: a chemometrical approach to ligand selectivity based on protein binding site analysis.

Article Details

Citation

Pirard B, Matter H

Matrix metalloproteinase target family landscape: a chemometrical approach to ligand selectivity based on protein binding site analysis.

J Med Chem. 2006 Jan 12;49(1):51-69.

PubMed ID
16392792 [ View in PubMed
]
Abstract

To gain insight into the structural determinants for the matrix metalloproteinase (MMP) family, we characterized the binding sites of 56 MMP structures and one TACE (tumor necrosis factor alpha converting enzyme) structure using molecular interaction fields (MIFs). These MIFs were produced by two approaches: the GRID force field and the knowledge-based potential DrugScore. The subsequent statistical analysis using consensus principal component analysis (CPCA) for the entire binding site and each subpockets revealed both approaches to encode similar information about discriminating regions. However, the relative importance of the probes varied between both approaches. The CPCA models provided the following ranking of the six subpockets based on the opportunity for selective interactions with different MMPs: S1' > S2, S3, S3' > S1, S2'. The interpretation of these models agreed with experimental binding modes inferred from crystal structures or docking.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
72 kDa type IV collagenaseP08253Details