Quantifying intrinsic specificity: a potential complement to affinity in drug screening.

Journal Article (Journal Article)

We report here the investigation of a novel description of specificity in protein-ligand binding based on energy landscape theory. We define a new term, intrinsic specificity ratio (ISR), which describes the level of discrimination in binding free energies of the native basin for a protein-ligand complex from the weaker binding states of the same ligand. We discuss the relationship between the intrinsic specificity we defined here and the conventional definition of specificity. In a docking study of molecules with the enzyme COX-2, we demonstrate a statistical correspondence between ISR value and geometrical shapes of the small molecules binding to COX-2. We further observe that the known selective (nonselective) inhibitors of COX-2 have higher (lower) ISR values. We suggest that intrinsic specificity ratio may be a useful new criterion and a complement to affinity in drug screening and in searching for potential drug lead compounds.

Full Text

Duke Authors

Cited Authors

  • Wang, J; Zheng, X; Yang, Y; Drueckhammer, D; Yang, W; Verkhivker, G; Wang, E

Published Date

  • November 9, 2007

Published In

Volume / Issue

  • 99 / 19

Start / End Page

  • 198101 -

PubMed ID

  • 18233118

International Standard Serial Number (ISSN)

  • 0031-9007

Digital Object Identifier (DOI)

  • 10.1103/PhysRevLett.99.198101


  • eng

Conference Location

  • United States