Shape Signatures is a new software technology that rapidly compares small-molecule compounds with each other, or with protein receptor sites, based on their shape, electrostatics, and other bio-relevant surface properties. Our primary goal in this R21 exploratory/developmental project is to transform this technology into an effective and general tool for computer-aided molecular design, to be provided as a cost-free resource to the academic community. Shape Signatures is extremely fast and easy to use in that it avoids specification of complex structural queries, protein docking, or molecular alignment schemes. Consequently, it is well-suited for deployment as a user-friendly web-based tool to be accessed by investigators with diverse backgrounds, ranging from bench scientists, to medicinal chemists, to computational specialists.
As Specific Aims, we will: 1) Enhance our large (5+ million compounds) and growing ligand-based Shape Signature databases to provide a unified cheminformatic resource for the research community; 2) Develop and deploy an improved receptor-based Shape Signature method to build receptor databases that are linked to the ligand databases; and 3) Integrate these tools within a user-friendly interface as a continuously-maintained web-based resource useful for drug discovery, fast virtual screening, and predictive toxicology. The primary goal of this R21 exploratory project is to transform the Shape Signatures technology into a comprehensive tool for computer-aided molecular design, to be provided as a cost-free resource to the academic scientific community. Success in this endeavor will provide researchers with an effective and user-friendly tool for numerous applications, including drug discovery, virtual screening, predictive toxicology. ? ? ?
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