Predicting experimental properties of integral membrane proteins by a naive Bayes approach.
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.
Martin-Galiano
Antonio J
AJ
Department of Genome Oriented Bioinformatics, Technische Universität München, Wissenchaftszentrum Weihenstephan, 85350 Freising, Germany.
Smialowski
Pawel
P
Frishman
Dmitrij
D
D000595:Amino Acid Sequence; D024361:Amino Acids, Basic; D001499:Bayes Theorem; D002965:Classification; D003001:Cloning, Molecular; D015870:Gene Expression; D057927:Hydrophobic and Hydrophilic Interactions; D008565:Membrane Proteins / Q000737:chemistry* / Q000145:classification; D012995:Solubility
D024361:Amino Acids, Basic; D008565:Membrane Proteins