Crystallographic Investigation of Ligand-Protein Interactions and Structure-aided Ligand Design
These researchers study the interactions in small molecule-macromolecular complexes of therapeutically important protein targets for use in structure-based drug/ligand design. Their primary experimental technique is X-ray crystallography, which requires significant computational resources. They are using MSI laboratories to assist in processing and analyzing multi-gigabyte data sets from diffraction data; they then use the processed data to determine the protein/complex structure. The structure is then finalized by iterative cycles of model fitting using graphic workstations and refinement. Experimental analyses are followed with the application of a variety of computational and visualization techniques to provide insights into the structural basis for ligand binding that can be applied to compound optimization and proposals for chemical synthesis. Completed structures will be prepared for deposition in the Research Collaboratory for Structural Bioinformatics database and for publication.
The Finzel laboratory is also committed to making structural data more readily available for use in structure-based design by providing novel web-based tools for protein structure superposition and comparative visualization. A database application that pulls together computational services for protein superposition based on substructure conformational matching and comprehensive substructure searching is supported. These tools support teaching and data management in structure-based drug design. A server provides access to these computational services. Future work may include investigating possible approaches to accelerating search services using high performance parallel computing.
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