MOTIVATION: Recently developed profile-profile methods rival structural comparisons in their ability to detect homology between distantly related proteins. Despite this tremendous progress, many genuine relationships between protein families cannot be recognized as comparisons of their profiles result in scores that are statistically insignificant. RESULTS: Using known evolutionary relationships among protein superfamilies in SCOP database, support vector machines were trained on four sets of discriminatory features derived from the output of HHsearch. Upon validation, it was shown that the automatic classification of all profile-profile matches was superior to fixed threshold-based annotation in terms of sensitivity and specificity. The effectiveness of this approach was demonstrated by annotating several domains of unknown function from the Pfam database. AVAILABILITY: Programs and scripts implementing the methods described in this manuscript are freely available from http://hhsvm.dlakiclab.org/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Abstract Two RNases, Dicer and Argonaute, are at the heart of the RNA interference (RNAi) molecular machinery responsible for gene silencing. Both RNases contain multiple domains, most of which have been characterized or have functions that can be predicted based on sequence comparisons. However, Dicers of higher eukaryotes contain the domain known as DUF283 which at present has no assigned role. Using sensitive profile–profile comparisons, we detected a divergent double-stranded RNA-binding domain coinciding with the DUF283 of Dicer. This finding has potential implications regarding the mechanistic role of Dicer in RNAi. Contact: [email protected] Supplementary information: Supplementary images are available at Bioinformatics online.

MOTIVATION: DIAMOD (Displayandmodeling ofDNA) was created as a user-friendly software for exploring and better understanding DNA structural variations, particularly DNA bending. It was intended to be as open as possible so that any of the existing or future predictive models can be used with it. RESULTS: DIAMOD features graphic display and interactive manipulation of DNA molecules on the screen. Since it works with di-, tri- or tetranucleotide models supplied as external files of angular parameters, it was recently used to evaluate critically all available predictive models for DNA bending. The program has a unique option to insert bends at defined positions in DNA sequence independently of the currently used model, which enables the simulation of both intrinsic and protein-induced kinking. Finally, many output file formats facilitate the sharing of data with other programs and the creation of visually pleasing images. AVAILABILITY: The program is available on request to academic users free of charge. It will be distributed via the WWW (http://www-personal.umich.edu/ mensur/software.html). Users with no network access can get a copy directly from the author. CONTACT: [email protected]