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Predicting experimental properties of integral membrane proteins by a naive Bayes approach
Author(s) -
MartinGaliano Antonio J.,
Smialowski Pawel,
Frishman Dmitrij
Publication year - 2008
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.21605
Subject(s) - discriminative model , bayes' theorem , computational biology , artificial intelligence , naive bayes classifier , pseudo amino acid composition , machine learning , biology , pattern recognition (psychology) , support vector machine , computer science , amino acid , bayesian probability , biochemistry , dipeptide
Integral membrane proteins (iMPs) are challenging targets for structure determination because of the substantial experimental difficulties involved in their sample preparation. Accordingly, success rates of large‐scale structural genomics consortia are much lower for this class of molecules compared to globular targets, underscoring the pressing need for predictive strategies to identify iMPs that are more likely to overcome laboratory bottlenecks. On the basis of the target status information available in the TargetDB repository, we describe the first large‐scale analysis of experimental behavior of iMPs. Using information on recalcitrant and propagating iMP targets as negative and positive sets, respectively, we present naive Bayes classifiers capable of predicting, from sequence alone, those proteins that are more amenable to cloning, expression, and solubilization studies. Protein sequences are represented in the space of 72 features, including amino acid composition, occurrence of amino acid groups, ratios between residue groups, and hydrophobicity measures. Taking into account unequal representation of main taxonomic groups in the TargetDB, sequence database had a beneficial effect on the prediction results. The classifiers achieve accuracies of 70%, 63–70%, and 61% in predicting the amenability of iMPs for cloning, expression, and solubilization, respectively, thus making them useful tools in target selection for structure determination. Our assessment of prediction results clearly demonstrates that classifiers based on single features do not possess acceptable discriminative power and that the experimental behavior of iMPs is imprinted in their primary sequence through relationships between a restricted set of key properties. In most cases, sets of 10–20 protein features were found actually relevant, most notably, the content of isoleucine, valine, and positively‐charged residues. Proteins 2008. © 2007 Wiley‐Liss, Inc.