Ongoing work in our laboratory has led to the development of two new enhanced chemical searching algorithms termed: (1) NOVA (Navigation and Optimization for Virtual Assembly), which can be used for fragment based de novo design and (2) CONGA (Construction by Genetic Algorithm), which can be used for evolution-based refinement. This presentation will focus on integration of NOVA and CONGA methods into the latest version of DOCK6, in preparation for an upcoming software release, and our experiences in testing and evaluating the code under different conditions. Outcomes of chemical and pose reproduction tests will be presented for 663 protein systems in which NOVA protocols were used in an attempt to re-grow cognate ligands in their native protein binding site using highly focused fragment libraries. Use of CONGA under different conditions to seed evolution of 1043 ligands in their respective crystallographic binding sites will also be presented to evaluate structural and energetic convergence over varying numbers of generations. Applications of both methods to design small molecule candidates that target fatty acid binding protein 5, a promising target to combat pain and inflammation, will also be discussed. <br/>

Refinement of protocols for de novo design and evolution-based refinement for DOCK: Application to fatty acid binding protein

256th National Meeting (2018)

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