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. It is important to determine the structures of peptides and proteins, so that structure-function relationship can be understood. Beta hairpin peptides are an important class of model peptides, as beta hairpin structures are present in a variety of biologically important proteins. Our laboratory has been focusing on determining the structures of beta hairpin peptides using vibrational circular dichroism (VCD) spectroscopy. In the past, the experimental VCD spectra are measured for a given peptide and the observed VCD spectral patterns are used to suggest the structure of peptides. In this qualitative interpretation process however several ambiguities remain because it is not clear if the observed spectral patterns are arising from the turn portion or from the beta sheet portion or both. More over there are several different types of beta turns and it is not clear which turn is responsible for the observed patterns. To avoid these ambiguities we are embarking on quantum mechanical calculations for beta hairpin peptides. Here the geometries of beta hairpin peptides will be optimized and VCD spectra are predicted at the optimized geometries. This process is repeated for all possible conformations and population weighted VCD spectrum is generated. If the predicted VCD spectra are in agreement with the experimentally observed VCD, then the structures used for calculations represent the structures of beta hairpin peptides used for solution state measurements. Even small beta hairpin peptides are too large for calculations on desktop computers. Thus supercomputer facilities are needed for calculating VCD spectra of beta hairpin peptides. In collaboration with Professor P. Balaram of I.I.Sc Bangalore, we measured the VCD spectra of smallest beta hairpin peptide, namely a tetrapeptide Boc-Trp-Aib-Gly-Trp-OMe, whose crystal structure indicates that this peptide adopts a type II-I beta-turn with two successive 4?1 hydrogen bonds. In solution, conformational inter-conversion between the form obtained in the crystal and a typical type I beta-turn might takes place. Even with a small 6-31G* basis set there are more than 700 basis functions for this molecule, so VCD calculations for this molecule cannot be completed on a desktop computer. We would like to carry out calculations on this peptide first. Then a few other beta hairpin peptides, namely Boc-Leu-Val-Val-DPro-LPro-Leu-Val-Val-OMe, Boc-Leu-Val-Val-Aib-DPro-Leu-Val-Val-OMe and Boc-Leu-Phe-Val-DPro-LPro-Leu-Phe-Val-OMe, for which we have recently reported the experimental VCD spectra will be investigated. For these calculations we will use Teragrid computer resources and Gaussian 03 program.
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