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Identifying cysteines and histidines in transition‐metal‐binding sites using support vector machines and neural networks
Author(s) -
Passerini Andrea,
Punta Marco,
Ceroni Alessio,
Rost Burkhard,
Frasconi Paolo
Publication year - 2006
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.21135
Subject(s) - histidine , chemistry , cysteine , artificial neural network , sequence (biology) , ligand (biochemistry) , amino acid , artificial intelligence , computer science , biochemistry , receptor , enzyme
Accurate predictions of metal‐binding sites in proteins by using sequence as the only source of information can significantly help in the prediction of protein structure and function, genome annotation, and in the experimental determination of protein structure. Here, we introduce a method for identifying histidines and cysteines that participate in binding of several transition metals and iron complexes. The method predicts histidines as being in either of two states (free or metal bound) and cysteines in either of three states (free, metal bound, or in disulfide bridges). The method uses only sequence information by utilizing position‐specific evolutionary profiles as well as more global descriptors such as protein length and amino acid composition. Our solution is based on a two‐stage machine‐learning approach. The first stage consists of a support vector machine trained to locally classify the binding state of single histidines and cysteines. The second stage consists of a bidirectional recurrent neural network trained to refine local predictions by taking into account dependencies among residues within the same protein. A simple finite state automaton is employed as a postprocessing in the second stage in order to enforce an even number of disulfide‐bonded cysteines. We predict histidines and cysteines in transition‐metal‐binding sites at 73% precision and 61% recall. We observe significant differences in performance depending on the ligand (histidine or cysteine) and on the metal bound. We also predict cysteines participating in disulfide bridges at 86% precision and 87% recall. Results are compared to those that would be obtained by using expert information as represented by PROSITE motifs and, for disulfide bonds, to state‐of‐the‐art methods. Proteins 2006. © 2006 Wiley‐Liss, Inc.