The Computational Chemical Biology (CCB) Core offers a variety of computational services which can be broken down into five categories:
Structure-based approaches: The CCB Core specializes in using state of the art virtual screening approaches to identify inhibitors of difficult, non-traditional drug targets such as protein-protein and protein-RNA interactions in addition to more traditional drug targets. These approaches allow screening ensembles of protein structures against very large compound libraries with up to millions of compounds. Additionally, the CCB Core offers the ability to screen against a libraries of virtual compounds given a set of reactions and available reactants to assist in fragment-based design and/or novel inhibitor discovery.
3D-ligand based approaches: The CCB Core offers virtual screens when an active conformation of a small molecule is known via ligand or receptor-based pharmacophores. Additionally, the CCB core has the capabilities through fragment replacement approaches that identify distinct scaffolds by replacing pieces of the active compound with alternative fragments that preserve the geometry of the active conformation.
Protein modeling: The CCB Core can leverage the Rosetta macromolecular modeling suite to perform protein modelling and design. If a sufficiently homologous protein structure exists in the PDB, the desired protein can be modelled using homology modelling. Likewise, Rosetta can be applied to protein design, such as optimizing a protein for stability or binding affinity to a protein, peptide, or peptidomimetics.
Chemoinformatics: The CCB Core will soon offer chemoinformatics approaches to assist in the drug design process. The CCB Core will offer clustering of hit compounds to identify common structural elements important for activity to suggest additional chemical structures for analog design and screening. Additionally, the CCB will offer quantitative structure-property (QSPR) analysis to identify chemical properties that are important for potency, ADME(T), or pharmacokinetic properties.
Computational expertise: The CCB core staff has a strong background in HPC and software development, including development within the Rosetta macromolecular modeling suite. The CCB offers custom algorithm/software/workflow development, database deployment, web application development, and hardware consultation.