Published online 3 June 2005
Article |
Prediction of solvent accessibility and sites of deleterious mutations from protein sequence
Department of Physics, Drexel University Philadelphia, PA 19104, USA 1Department of Physics and Institute of Molecular Biophysics and School of Computational Science, Florida State University Tallahassee, FL 32306, USA
*To whom correspondence should be addressed. Tel: +1 850 645 1336; Fax: +1 850 644 7244; Email: zhou{at}sb.fsu.edu
Received March 2, 2005. Revised April 29, 2005. Accepted May 16, 2005.
Residues that form the hydrophobic core of a protein are critical for its stability. A number of approaches have been developed to classify residues as buried or exposed. In order to optimize the classification, we have refined a suite of five methods over a large dataset and proposed a metamethod based on an ensemble average of the individual methods, leading to a two-state classification accuracy of 80%. Many studies have suggested that hydrophobic core residues are likely sites of deleterious mutations, so we wanted to see to what extent these sites can be predicted from the putative buried residues. Residues that were most confidently classified as buried were proposed as sites of deleterious mutations. This proposition was tested on six proteins for which sites of deleterious mutations have previously been identified by stability measurement or functional assay. Of the total of 130 residues predicted as sites of deleterious mutations, 104 (or 80%) were correct.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  N. Tuncbag, G. Kar, O. Keskin, A. Gursoy, and R. Nussinov A survey of available tools and web servers for analysis of protein-protein interactions and interfaces Brief Bioinform, May 1, 2009; 10(3): 217 - 232. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Wu and Y. Zhang A comprehensive assessment of sequence-based and template-based methods for protein contact prediction Bioinformatics, April 1, 2008; 24(7): 924 - 931. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Qin and H.-X. Zhou meta-PPISP: a meta web server for protein-protein interaction site prediction Bioinformatics, December 15, 2007; 23(24): 3386 - 3387. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Tjong, S. Qin, and H.-X. Zhou PI2PE: protein interface/interior prediction engine Nucleic Acids Res., July 13, 2007; 35(suppl_2): W357 - W362. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Park and V. Helms On the derivation of propensity scales for predicting exposed transmembrane residues of helical membrane proteins Bioinformatics, March 15, 2007; 23(6): 701 - 708. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Tjong and H.-X. Zhou DISPLAR: an accurate method for predicting DNA-binding sites on protein surfaces Nucleic Acids Res., March 12, 2007; 35(5): 1465 - 1477. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Mononen, E. H. Seppala, P. Duggal, V. Autio, T. Ikonen, P. Ellonen, J. Saharinen, J. Saarela, M. Vihinen, T. L.J. Tammela, et al. Profiling Genetic Variation along the Androgen Biosynthesis and Metabolism Pathways Implicates Several Single Nucleotide Polymorphisms and Their Combinations as Prostate Cancer Risk Factors Cancer Res., January 15, 2006; 66(2): 743 - 747. [Abstract] [Full Text] [PDF]
|
|