Fluorescence spectroscopy of the amino acid, tryptophan, is a convenient, rapid and user- friendly tool for studying the structure and function of disease-related proteins. The technique is also among the most sensitive. As the diffraction limit to image resolution is breached, imaging of fluorescent single molecules becomes possible. Indeed, single molecule imaging opens the possibility of a movie of the cell, and therefore molecular level understanding of cellular processes. The current level of spectral interpretation for tryptophan, however, is far from the molecular level. This is because tryptophan fluorescence data is complicated by several overlying factors, which include solvent relaxation, multiple conformers, and nonradiative decay. The proposed research addresses the low resolution of data interpretation for tryptophan fluorescence through both molecular dynamics simulation and spectroscopic methods. The goal of the research is to create a matrix of fluorescence spectral parameters that will constitute a 'fingerprint' for specific tryptophan environments and conformations within proteins. With an improvement in spectral interpretation, this work will impact on human health and well-being, both directives of the NIH, because understanding of protein function, and therefore, drug interaction with disease-related proteins, will be greatly improved, cutting the time to drug development.
Understanding the structure of disease-related proteins is necessary for the design of effective drugs. The natural amino acid, tryptophan, fluoresces, and therefore can be used as a probe of protein structure. This project will improve the interpretation of tryptophan fluorescence spectra, providing the molecular-level detail necessary for design of drugs to improve human health.
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|Grigoryan, Alexandre; Eisenberg, Azaria S; Juszczak, Laura J (2017) PHOXI: A High Quantum Yield, Solvent-Sensitive Blue Fluorescent 5-Hydroxytryptophan Derivative Synthesized within Ten Minutes under Aqueous, Ambient Conditions. J Phys Chem B 121:7256-7266|
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|Eisenberg, Azaria Solomon; Juszczak, Laura J (2014) The broken ring: reduced aromaticity in Lys-Trp cations and high pH tautomer correlates with lower quantum yield and shorter lifetimes. J Phys Chem B 118:7059-69|
|Eisenberg, Azaria Solomon; Juszczak, Laura J (2013) Relating Trp-Glu dipeptide fluorescence to molecular conformation: the role of the discrete Chi 1 and Chi 2 angles. J Comput Chem 34:1549-60|