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Predicting DNA‐binding amino acid residues from electrostatic stabilization upon mutation to Asp/Glu and evolutionary conservation
Author(s) -
Chen Yao Chi,
Wu Chih Yuan,
Lim Carmay
Publication year - 2007
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.21366
Subject(s) - dna , mutation , residue (chemistry) , conserved sequence , chemistry , amino acid , binding site , biophysics , cluster (spacecraft) , amino acid residue , static electricity , dna binding site , biochemistry , peptide sequence , biology , gene , base sequence , physics , programming language , quantum mechanics , promoter , gene expression , computer science
Binding of polyanionic DNA depends on the cluster of electropositive atoms in the binding site of a DNA‐binding protein. Such a cluster of electropositive protein atoms would be electrostatically unfavorable without stabilizing interactions from the respective electronegative DNA atoms and would likely be evolutionary conserved due to its critical biological role. Consequently, our strategy for predicting DNA‐binding residues is based on detecting a cluster of evolutionary conserved surface residues that are electrostatically stabilized upon mutation to negatively charged Asp/Glu residues. The method requires as input the protein structure and sufficient sequence homologs to define each residue's relative conservation, and it yields as output experimentally testable residues that are predicted to bind DNA. By incorporating characteristic DNA‐binding site features (i.e., electrostatic strain and amino acid conservation), the new method yields a prediction accuracy of 83%, which is much higher than methods based on only electrostatic strain (57%) or conservation alone (50%). It is also less sensitive to protein conformational changes upon DNA binding than methods that mainly depend on the 3D protein structure. Proteins 2007. © 2007 Wiley‐Liss, Inc.