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PMID: 15937195 Published · epublish English Evaluation Study Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, P.H.S.

Prediction of solvent accessibility and sites of deleterious mutations from protein sequence.

Nucleic acids research ·Vol. 33 ·No. 10 ·2005-00-00 ·Pages 3193-9

Chen H, Zhou HX

Abstract

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.

MeSH Terms
Amino Acid Sequence Amino Acids/chemistry,classification Hydrophobic and Hydrophilic Interactions Molecular Sequence Data Mutation Proteins/chemistry,genetics Reproducibility of Results Sequence Analysis, Protein/methods Solvents/chemistry
Chemicals
Amino Acids Proteins Solvents
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Chen Huiling
Department of Physics, Drexel University Philadelphia, PA 19104, USA.
Zhou Huan-Xiang
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
DOI
10.1093/nar/gki633
Published
2005-00-00
Epub
2005-00-03
Pages
3193-9
Language
English
Region
England
NLM ID
0411011
PMCID
PMC1142490
Subset
IM
Grants
NIGMS NIH HHS · R01 GM058187 · United States
NIGMS NIH HHS · GM58187 · United States
External Links
PubMed source DOI: 10.1093/nar/gki633 PMC Full Text View journal details
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