ORFeus: Detection of distant homology using sequence profiles and predicted secondary structure.

ORFeus is a fully automated, sensitive protein sequence similarity search server available to the academic community via the Structure Prediction Meta Server (http://BioInfo.PL/Meta/). The goal of the development of ORFeus was to increase the sensitivity of the detection of distantly related protein families. Predicted secondary structure information was added to the information about sequence conservation and variability, a technique known from hybrid threading approaches. The accuracy of the meta profiles created this way is compared with profiles containing only sequence information and with the standard approach of aligning a single sequence with a profile. Additionally, the alignment of meta profiles is more sensitive in detecting remote homology between protein families than if aligning two sequence-only profiles or if aligning a profile with a sequence. The specificity of the alignment score is improved in the lower specificity range compared with the robust sequence-only profiles.