Fundamental Predictions of Tryptophan Emission Spectra in Proteins

Montana State University, Bozeman MT

Investigators

Abstract

The objective of this research, funded by the Division of Molecular and Cellular Biosciences and the Division of Chemistry, is to use an integrated approach of theory and computation to understand variations in quantum yield of tryptophan fluorescence in proteins. A custom hybrid quantum mechanical-molecular dynamics method will be applied to the higher charge transfer excited states instead of the electrostatic effects on fluorescence wavelength from the 1La state to predict tryptophan fluorescence wavelength shifts due to protein electric fields and solvation. The study will consider the possibility of both short and long-range electron transfer to (or from) at least the following implicated sources: the peptide backbone, protonated carboxylates (Glu and Asp), amide side chains (Asn and Gln), histidine, cysteine, disulfide bonds, and aromatic groups. The goal is to determine if there exists a correlation between fluorescence quantum yield and the incidence of charge transfer states that are particularly low in energy due to extreme electrostatic potential differences and/or propitious solvation, using semiempirical and ab initio quantum mechanics applied to super molecular pairs consisting of tryptophan and a putative electron acceptor/donor. At least 20 proteins with a full range of quantum yields, along with well-studied model compounds will be included in the study. Insight into the details of quenching is of practical importance because the protein fluorescence is used routinely by scientists to follow a myriad of transformations involving structural changes in the protein, for example, folding, unfolding, ligand binding, redox reactions, binding to other proteins, etc., all dynamic events for which structural information is often lacking. This work should add new and useful knowledge to the field of long-range electron transfer in proteins, which is central to photosynthesis and bioenergetics.