Dr. Alex Brown is a theoretical and computational chemist currently teaching and conducting research at The University of Alberta. Dr. Brown joined the Faculty of Chemistry in 2003; before which he conducted research at University of Bristol in Bristol, U.K. (1997-1999), Emory University in Atlanta, USA (2002-2003). Dr. Brown obtained his PhD from The University of Waterloo in 1997. His research includes: computational design of small-molecule biofluorophores; understanding of novel bonding and structure of inorganic materials; photochemistry and photophysics of fluorescent proteins; theoretical/computational studies of molecular photochemistry and laser control; optimal control theory for laser control; and molecular quantum dynamics.
Professor of Theoretical and Computational Chemistry
Department of Chemistry, University of Alberta
“Two-Photon Absorption in Fluorescent Proteins: Computational Design of New Chromophores”
Two-photon absorption (TPA) microscopy of fluorescent proteins (FPs) is a powerful bio-imaging tool. However, TPA probes are usually associated with less sensitivity than their one -photon absorption alternatives. Thus, designing fluorophores with large TPA cross sections is an important area of research. While non-canonical amino acids (ncAAs) have been utilized for designing proteins with novel properties, they have not been widely exploited for developing fluorescent proteins, including those designed specifically for TPA. In this talk, I will introduce TPA, including the use of two – (or few-) level models for interpreting TPA cross-sections, based on underlying molecular properties. I will highlight our recent work computationally exploring TPA in FP chromophores, including those incorporating ncAAs. Time-dependent density functional theory (TD-DFT) has been used to screen possible green FP(GFP)- and red FP(RFP)-like chromophores made from non -canonical amino acids. Overall, a number of new FP chromophores built from ncAAs, with large intrinsic TPA as compared to known FP chromophores, have been proposed and the strong effect of conformation on TPA explored. If time permits, I will discuss ongoing work examining TPA in the goldFP, as well as alternative approaches to TD-DFT for determing the TPA cross-sections