Assigning functional properties to a newly discovered protein is a key challenge in modern biology. To this end, computational modeling of the three-dimensional atomic arrangement of the amino acid chain is often crucial in determining the role of the protein in biological processes. We present a community-wide web-based protocol, RaptorX server ( http://raptorx.uchicago.edu ), for automated protein secondary structure prediction, template-based tertiary structure modeling, and probabilistic alignment sampling.Given a target sequence, RaptorX server is able to detect even remotely related template sequences by means of a novel nonlinear context-specific alignment potential and probabilistic consistency algorithm. Using the protocol presented here it is thus possible to obtain high-quality structural models for many target protein sequences when only distantly related protein domains have experimentally solved structures. At present, RaptorX server can perform secondary and tertiary structure prediction of a 200 amino acid target sequence in approximately 30 min.

The National Microbial Pathogen Data Resource (NMPDR) () is a National Institute of Allergy and Infections Disease (NIAID)-funded Bioinformatics Resource Center that supports research in selected Category B pathogens. NMPDR contains the complete genomes of ∼50 strains of pathogenic bacteria that are the focus of our curators, as well as >400 other genomes that provide a broad context for comparative analysis across the three phylogenetic Domains. NMPDR integrates complete, public genomes with expertly curated biological subsystems to provide the most consistent genome annotations. Subsystems are sets of functional roles related by a biologically meaningful organizing principle, which are built over large collections of genomes; they provide researchers with consistent functional assignments in a biologically structured context. Investigators can browse subsystems and reactions to develop accurate reconstructions of the metabolic networks of any sequenced organism. NMPDR provides a comprehensive bioinformatics platform, with tools and viewers for genome analysis. Results of precomputed gene clustering analyses can be retrieved in tabular or graphic format with one-click tools. NMPDR tools include Signature Genes, which finds the set of genes in common or that differentiates two groups of organisms. Essentiality data collated from genome-wide studies have been curated. Drug target identification and high-throughput, in silico, compound screening are in development.

The National Microbial Pathogen Data Resource (NMPDR, http://www.nmpdr.org) identifies candidate drug targets and virtually screens potential drugs. NMPDR is one of eight Bioinformatic Resource Centers (BRC) established by NIAID to support research on potential agents of biowarfare, bioterrorism, or emerging disease. Candidate targets are essential for growth or virulence in at least one NMPDR focus organism, have been included in biological subsystems by NMPDR curators, have orthologs with experimentally determined structures in Protein Data Bank, and have orthologs in a substantial number of bacterial Priority Pathogens curated by the BRCs. In silico screening is the computational molecular docking of a library of ligands against a protein structure using a force field method to compute the binding energy. Targets are first docked with 1.5K randomly selected compounds. The results are used as a training set for a neural network that evaluates the characteristics of binding and non‐binding compounds. Libraries of commercially available or FDA approved drug compounds are screened with the neural net to select an enriched set of probable ligands. Molecular docking is then performed with the selected compounds using Dock5 on a BlueGene supercomputer. The top 1000 docked compounds are posted on NMPDR as targets are screened. Funded by NIAID under Contract No. HHSN266200400042C.