The function of proteins is governed by their three-dimensional structure. A full understanding of protein function thus requires understanding the principles underlying protein structure. This project aims at understanding factors influencing secondary structure formation in proteins by using simple peptide models of secondary structural elements. Our project focuses on both kinetic and equilibrium studies of peptide structure. In collaboration with the laboratory of Prof. David Kliger, UC Santa Cruz, we have developed a peptide system that displays a photoactivated beta sheet to alpha helix transition. We are planning to follow the kinetics of sheet to helix folding by transient circular dichroism spectroscopy. The structure of the sheet form of the peptide has been characterized by Fourier transform infrared and circular dichroism spectroscopies. The helix form of the peptide is amenable to study by nuclear magnetic resonance as well, and has been characterized by NOESY and other multi-dimensional magnetic resonance experiments, in addition to FTIR and CD methods. In addition to the kinetic studies on the rate of secondary structure interconversion, we are also studying factors which cause a transition from sheet to helix in equilibrium states of the peptide. This transition can be caused by changes in pH, temperature, salt concentration, or peptide concentration. The facilities of the Computer Graphics Lab are used to visualize the three-dimensional structure of the beta sheet and alpha helix, with particular emphasis on the interactions of amino acid side chains that play a role in stabilizing beta sheet versus helical structures in the different forms of the peptide. CGL programs (in particular, MidasPlus) and facilities have been critical in designing the peptides used in our studies. Graphical displays of the peptides, comparison of model peptide structures to experimental structures found in the Protein Data Bank, and visualization of small molecule structures from the Cambridge Crystal Database are a few examples of how the graphics facilities at the CGL have been utilized. Other uses of programs and databases supported by the CGL include comparison of designed peptide sequences to known protein and peptide sequences.
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