RESUMEN
PD-(D/E)XK nucleases, initially represented by only Type II restriction enzymes, now comprise a large and extremely diverse superfamily of proteins. They participate in many different nucleic acids transactions including DNA degradation, recombination, repair and RNA processing. Different PD-(D/E)XK families, although sharing a structurally conserved core, typically display little or no detectable sequence similarity except for the active site motifs. This makes the identification of new superfamily members using standard homology search techniques challenging. To tackle this problem, we developed a method for the detection of PD-(D/E)XK families based on the binary classification of profile-profile alignments using support vector machines (SVMs). Using a number of both superfamily-specific and general features, SVMs were trained to identify true positive alignments of PD-(D/E)XK representatives. With this method we identified several PFAM families of uncharacterized proteins as putative new members of the PD-(D/E)XK superfamily. In addition, we assigned several unclassified restriction enzymes to the PD-(D/E)XK type. Results show that the new method is able to make confident assignments even for alignments that have statistically insignificant scores. We also implemented the method as a freely accessible web server at http://www.ibt.lt/bioinformatics/software/pdexk/.
Asunto(s)
Inteligencia Artificial , Endonucleasas/clasificación , Alineación de Secuencia/métodos , Secuencia de Aminoácidos , Dominio Catalítico , Secuencia Conservada , Enzimas de Restricción del ADN/química , Enzimas de Restricción del ADN/clasificación , Endonucleasas/química , Exonucleasas/clasificación , Resolvasas de Unión Holliday/química , Datos de Secuencia Molecular , Estructura Terciaria de Proteína , Homología de Secuencia de Aminoácido , Programas InformáticosRESUMEN
SUMMARY: Detection of distant homology is a widely used computational approach for studying protein evolution, structure and function. Here, we report a homology search web server based on sequence profile-profile comparison. The user may perform searches in one of several regularly updated profile databases using either a single sequence or a multiple sequence alignment as an input. The same profile databases can also be downloaded for local use. The capabilities of the server are illustrated with the identification of new members of the highly diverse PD-(D/E)XK nuclease superfamily. AVAILABILITY: http://www.ibt.lt/bioinformatics/coma/