This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The research capability provided by the Core helps investigators to understand structural aspects of biological activities of proteins. The genome sequencing projects are providing vast quantities of new information that is invaluable for identifying and characterizing gene products. However, primary structure is only part of the complete structural characterization required for understanding mechanisms of protein functions. The three-dimensional (3D) structures must also be known. For initial structure-function studies, fragments/domains of proteins can be efficiently synthesized using solid phase peptide synthesis. These fragments could be structural, functional domains or epitopes for raising antibodies. The selection of fragments/domains is done by using structural bioinformatics tools. 3D structural characterizations of proteins, protein fragments and synthetic polypeptides is done in solution using chiroptic spectroscopy (ECD and VCD). These methodologies, although at low resolution, provide the initial structural information and help to other high resolution techniques to determine the finer structure. Structures obtained with ECD and VCD spectroscopy are further characterized with molecular dynamics (MD) simulations to reveal fine structural details and structural stabilities. Furthermore, homology modeling and molecular docking complemented with MD simulations is used to design of functional analogs of interacting domains of polypeptides and proteins.
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