A threading-based method (FINDSITE) for ligand-binding site prediction and functional annotation.

A threading-based method (FINDSITE) for ligand-binding site prediction and functional annotation. Research Abstract Details 

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A threading-based method (FINDSITE) for ligand-binding site prediction and functional annotation. Abstract Text:

Michal Brylinski,Jeffrey Skolnick,Michal Brylinski,Jeffrey Skolnick,

The detection of ligand-binding sites is often the starting point for protein function identification and drug discovery. Because of inaccuracies in predicted protein structures, extant binding pocket-detection methods are limited to experimentally solved structures. Here, FINDSITE, a method for ligand-binding site prediction and functional annotation based on binding-site similarity across groups of weakly homologous template structures identified from threading, is described. For crystal structures, considering a cutoff distance of 4 A as the hit criterion, the success rate is 70.9% for identifying the best of top five predicted ligand-binding sites with a ranking accuracy of 76.0%. Both high prediction accuracy and ability to correctly rank identified binding sites are sustained when approximate protein models (<35% sequence identity to the closest template structure) are used, showing a 67.3% success rate with 75.5% ranking accuracy. In practice, FINDSITE tolerates structural inaccuracies in protein models up to a rmsd from the crystal structure of 8-10 A. This is because analysis of weakly homologous protein models reveals that about half have a rmsd from the native binding site <2 A. Furthermore, the chemical properties of template-bound ligands can be used to select ligand templates associated with the binding site. In most cases, FINDSITE can accurately assign a molecular function to the protein model.

A threading-based method (FINDSITE) for ligand-binding site prediction and functional annotation. Publishing Authors By Initials

M Brylinski,J Skolnick,M Brylinski,J Skolnick,

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A threading-based method (FINDSITE) for ligand-binding site prediction and functional annotation. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Proceedings of the National Academy of Sciences of

VOLUME: 105

Page Numbers: 129-34

Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

ISSN: 1091-6490

DAY: 28

MONTH: 12

YEAR: 2007

A threading-based method (FINDSITE) for ligand-binding site prediction and functional annotation. Information

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LANGUAGE: eng

NlmUniqueID: 7505876

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Grant and Affiliation Information for A threading-based method (FINDSITE) for ligand-binding site prediction and functional annotation.

AFFILIATION: Center for the Study of Systems Biology, School of Biology, Georgia Institute of Technology, 250 14th Street NW, Atlanta, GA 30318, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: GM-48835

ACRONYM: GM

MEDLINETA: Proc Natl Acad Sci U S A

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