Thus excellent in vitro and in vivo activities and high selectivity of aforementioned compounds merit further investigation in order to reduce the cytotoxicity that may result in development of newer anti-trypanosomal drug with reduced toxicity, improved efficacy and pharmacokinetic profile. As the drug discovery and development process is expensive in terms of time and money, the cross application of existing series of compounds with selective trypanocidal activity may be the best prospect to new anti-trypanosomal drugs in the short term. More emphasis has to be put in the field of CADD approaches for development of anti-trypanosomal agents as CADD study reduces the time and cost required for development of newer analogues. NoD: a Nucleolar localization sequence detector for eukaryotic and viral proteins BACKGROUND: Nucleolar localization sequences (NoLSs) are short targeting sequences responsible for the localization of proteins to the nucleolus. Given the large number of proteins experimentally detected in the nucleolus and the central role of this subnuclear compartment in the cell, NoLSs are likely to be important regulatory elements controlling cellular traffic. Although many proteins have been reported to contain NoLSs, the systematic characterization of this group of targeting motifs has only recently been carried out. RESULTS: Here, we describe NoD, a web server and a command line program that predicts the presence of NoLSs in proteins. Using the web server, users can submit protein sequences through the NoD input form and are provided with a graphical output of the NoLS score as a function of protein position. While the web server is most convenient for making prediction for just a few proteins, the command line version of NoD can return predictions for complete proteomes. NoD is based on our recently described human-trained artificial neural network predictor. Through stringent independent testing of the predictor using available experimentally validated NoLS-containing eukaryotic and viral proteins, the NoD sensitivity and positive predictive value were estimated to be 71% and 79% respectively. CONCLUSIONS: NoD is the first tool to provide predictions of nucleolar localization sequences in diverse eukaryotes and viruses. NoD can be run interactively online at http://www.compbio.dundee.ac.uk/nod or downloaded to use locally. The nucleolus is a sub-nuclear cellular compartment that is accessible to a large number of proteins since it is not surrounded by a membrane. To date, over 4500 distinct human proteins have been identified from purified nucleoli [1] . The most well-characterized function of the nucleolus is the biogenesis of ribosomes [2] . However, nucleolar proteins are diverse and dynamic, reflecting the central role of this compartment in the cell through its involvement in numerous other key cellular processes and in the cellular response to changing conditions [3] [4] [5] [6] [7] . Indeed, many proteins have been found to localize cyclically or conditionally to the nucleolus [3, 4, 7, 8] .