Document Detail


Robust recognition of zinc binding sites in proteins.
MedLine Citation:
PMID:  18042678     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Metals play a variety of roles in biological processes, and hence their presence in a protein structure can yield vital functional information. Because the residues that coordinate a metal often undergo conformational changes upon binding, detection of binding sites based on simple geometric criteria in proteins without bound metal is difficult. However, aspects of the physicochemical environment around a metal binding site are often conserved even when this structural rearrangement occurs. We have developed a Bayesian classifier using known zinc binding sites as positive training examples and nonmetal binding regions that nonetheless contain residues frequently observed in zinc sites as negative training examples. In order to allow variation in the exact positions of atoms, we average a variety of biochemical and biophysical properties in six concentric spherical shells around the site of interest. At a specificity of 99.8%, this method achieves 75.5% sensitivity in unbound proteins at a positive predictive value of 73.6%. We also test its accuracy on predicted protein structures obtained by homology modeling using templates with 30%-50% sequence identity to the target sequences. At a specificity of 99.8%, we correctly identify at least one zinc binding site in 65.5% of modeled proteins. Thus, in many cases, our model is accurate enough to identify metal binding sites in proteins of unknown structure for which no high sequence identity homologs of known structure exist. Both the source code and a Web interface are available to the public at http://feature.stanford.edu/metals.
Authors:
Jessica C Ebert; Russ B Altman
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2007-11-27
Journal Detail:
Title:  Protein science : a publication of the Protein Society     Volume:  17     ISSN:  0961-8368     ISO Abbreviation:  Protein Sci.     Publication Date:  2008 Jan 
Date Detail:
Created Date:  2007-12-24     Completed Date:  2008-03-06     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  9211750     Medline TA:  Protein Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  54-65     Citation Subset:  IM    
Affiliation:
Department of Genetics, Stanford University, Stanford, California 94305, USA.
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MeSH Terms
Descriptor/Qualifier:
Binding Sites
Carrier Proteins / chemistry*,  genetics,  metabolism*
Genomics
Models, Biological
Models, Molecular
Protein Conformation
Sensitivity and Specificity
Zinc / chemistry*,  metabolism*
Grant Support
ID/Acronym/Agency:
LM05652/LM/NLM NIH HHS
Chemical
Reg. No./Substance:
0/Carrier Proteins; 7440-66-6/Zinc
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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