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Introduction Access to protein structural information enables rational experimental design across all life-science disciplines. The advent of high throughput gene sequencing is spawning a structural information explosion in the biological sciences. The total repertoire of protein structures useful or interesting to life science researchers will ultimately be numbered in the millions. Historically, protein structure has been accessed through physical methods such as X-ray crystallography and computational methods such as homology modeling. Conventional homology modeling generally provides good protein-core structures but often highly inaccurate surface structural information. Unfortunately, nearly all of the pharmacologically important structural information resides on the protein surface. At the same time, a recent systematic study of the applicability of X-ray crystallography has shown that today only a few percent of proteins actually yield X-ray diffracting crystals suitable for structure determination. Consequently, computational methods offer the only practical promise of accessing and using the full potential of protein structural information on a large scale at the present time, and possibly well into the future. Fortunately, steady advances in computational modeling technologies, rapidly declining costs for computationally intensive calculations, and NIH sponsored structural proteomics initiative, are coalescing to solve this problem. Industrial Scale Protein Structure Generation and Advanced Structural Data Mining Tools SBI's ProMax™ Augmented Homology Modeling™ Technology - Instant, large-scale access to X-ray quality structures, on demand SBI’s patented or otherwise proprietary computational methodologies permit the accurate generation of not only the core structure, but of the critical protein surface structure as well for many thousands of proteins in more than 450 distinct protein structural families to date. The number of structural families to which our technology applies is growing. The NIH’s multi-hundred million dollar protein structure initiative to make available 10,000 additional protein structures over the next five years will allow continued expansion of our proprietary structural offerings. SBI uses a suite of proprietary technologies for structure and function-based alignment, fold prediction, true ab initio loop generation, core structure corrections, extensive refinement, to generate structures that are comparable in quality to those obtained directly through X-ray crystallography, at a fraction of the cost and time required for X-ray crystallography. SBI’s proprietary Augmented Homology Modeling™ technology requires at least one X-ray crystallographic structure within a protein fold family in order to generate structures for the remaining family members. This information is obtained from a variety of sources including public, academic, and in-house X-ray crystallography efforts. ProMax™ Drug-Target Database - Multiplying the impact of your modeling resources Variome™ Drug-Target Specific Polymorphism Structural Database Modules - For "Best in Class" and "Next Generation" Drugs SBI’s Variome database modules consist of large-scale drug target specific collections of high-quality protein structures generated from the genetic sequence variants (polymorphisms) from tens of thousands of individuals. The HIV-Reverse Transcriptase and HIV-Protease modules are the first two modules developed in partnership with Quest Diagnostics. Variome™ modules provide a definitive understanding of the shape repertoire of structural variations of drug targets within the potential patient population, which is critical to optimal drug design.™ StructureBank™, Enterprise-wide or Program-wide Storage, Comparative Analysis, and Data Sharing Solution - Bringing 3D Protein Structure to the Experimentalist's Desktop Drug Discovery Technologies, Services, and Collaborations DynaPharm® Technology - Genes to Leads® in 60-120 Days DynaPharm templates are virtual constructs of active sites of proteins derived from dynamic simulations of the changes in flexible protein shape (essentially molecular “movies”) that predict the 3D molecular characteristics of likely drug leads. DynaPharm® templates are used to computationally screen and select active molecules from SBI’s CombiLib database (a virtual library of millions of drug-like small-molecule 3D structures), the ChemNavigator collection of approximately 2 million compounds, the Available Chemicals Directory, your in-house compound collection, or from any other properly formatted compound collection. This process yields typical “hit rates” of 10%, in marked contrast to 0.01% to 0.001% for typical high-throughput screening – a 1,000-fold to 10,000-fold reduction in the number of compounds needed to be acquired or synthesized and tested. The process is quick (i.e., 60-120 days), applicable simultaneously to numerous targets, and thus well suited to handle the challenge posed by the advent of thousands of potential new drug targets emerging from genomics efforts.®® CombiLib® Technology Drug Discovery Collaborations SBI uses its DynaPharm and CombiLib in silico screening technologies to rapidly generate drug leads for pharmaceutical and biotech corporate partners. The process has already yielded active initial drug leads for ten different drug targets in many therapeutic categories from public or privately provided gene sequences in 60-120 days, with hit rates of approximately 10%. SBI has successfully attracted collaborative partners in North America and Japan.®® Advanced Structural Bioinformatics Data Mining Technologies SBI has a broad range of proprietary structural bioinformatics tools and technologies. Included among them are: AutoModel™ and ProteoMine™ automated structure prediction and annotation tools suite; ASTER technology for dramatically accelerated X-ray and NMR-based structure determination, using a patented non-linear recursive filter; DBA™ application-specific and customizable discrete Bayesian algorithm for pattern recognition and data fusion technology (e.g., gene expression and protein expression analysis, toxicity profiling, presymptomatic disease diagnosis, identifying new clinical indications from Phase III/IV data, function prediction from structure, analysis of adverse drug reaction data); drug likeness prediction methods using novel proprietary descriptors; microarray noise and artifact suppression, based upon aerospace stellar background noise suppression algorithms; and proprietary leading edge secondary structure and automated alignment prediction algorithms.™ Intellectual Property The Company aggressively protects in intellectual property through patent filings and other means. SBI has a number of issued and/or filed US and foreign patent applications, has a number of applications in preparation, and has licensed certain intellectual property covering protein structure, and the generation, use, refinement, data mining, interpretation, and distribution means for protein structure and other bioinformatics related data. Additionally, the Company has filed and intends to continue to file, US patent applications with regard to the interaction of certain compounds (including composition of matter) with specified drug targets.
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