Monday, March 4, 2013 - 16:00 to 17:00
Weniger 153
Event Speaker: 
Prof. Andrew H. Marcus, Department of Chemistry, Oregon Center for Optics, Institute of Molecular Biology, University of Oregon
Local Contact: 
Michael Zwolak

The properties of biological macromolecules are greatly influenced by local soft interactions between proteins, nucleic acids, sugars and lipids. Such interactions affect the stability of biomolecular complexes, as well as the barriers that must be surmounted for molecular motions to occur. In this talk, I will present fluorescence based nonlinear spectroscopic measurements that determine the three-dimensional shapes, or local conformations, adopted by electronically coupled molecular dimers in biological environments. I will describe studies of the assembly of dimers of square-shaped metal tetraphenyl porphyrin (TPP) molecules embedded in a phospholipid bilayer membrane, in which we show that the assembled dimers exist as a “T-shaped” structure [1-3]. When a flexible linker is used to connect two TPP molecules, the “folded” form of the dimer is favored at elevated temperatures, which we show is due to entropic interactions between the TPP molecules and the local membrane environment. Similar experiments performed on dimers of fluorescent nucleic acid bases, which may be substituted for natural bases within model DNA constructs, reveal the structures of local base stacking conformations, and provide information about the balance of thermodynamic forces that contribute to nucleic acid stability [4-6]. Finally, I will describe our recent single-molecule fluorescence experiments to investigate DNA ‘breathing’ fluctuations, in which nucleotide residues near single-stranded (ss) – double-stranded (ds) DNA forks and junctions temporarily adopt local conformations that depart from their most stable structures. It is thought that the transient occurrences of ‘open’ conformations are of central importance to the function of DNA-protein complexes responsible for replication, transcription, and other reactions that involve the manipulation of the DNA genome [7].


1. Lott, G. A.; Perdomo-Ortiz, A.; Utterback, J. K.; Widom, J. R.; Aspuru-Guzik, A.; Marcus, A. H. “Conformation of Self-Assembled Porphyrin Dimers in Liposome Vesicles by Phase-Modulation 2D Fluorescence Spectroscopy,” Proc. Nat. Acad. Sci., 2011, 108, 16521-16526.

2. Perdomo, A.; Widom, J. R.; Lott, G. A.; Aspuru-Guzik, A.; Marcus, A. H. “Conformation and Electronic Population Transfer in Membrane Supported Self-Assembled Porphyrin Dimers by Two-Dimensional Fluorescence Spectroscopy,” J. Phys. Chem. B 2012, 116, 10757-10770.

3. Widom, J. R.; Perdomo-Ortiz, A.; Lee, W.; Rappoport, D.; Molinski, T. F.; Aspuru-Guzik, A.; Marcus, A. H. “Temperature-Dependent Conformations of a membrane supported ‘zinc porphyrin tweezer’ by 2D Fluorescence Spectroscopy,” (manuscript submitted January 13, 2013, revision submitted February 22, invited paper for Prof. John C. Wright Festschrift special issue to appear in the Journal of Physical Chemistry A).

4. Datta, K.; Johnson, N. P.; Villani, G.; Marcus, A. H.; von Hippel, P. H. “Characterization of the 6-Methyl Isoxanthoptherin (6-MI) Base Analogue Dimer, A Spectroscopic Probe for Monitoring Guanine Base Conformation at Specific Sites in Nucleic Acids,” Nucl. Acids Res., 2012, 40, 1191-202.

5. Widom, J. R.; Rappoport, D.; Perdomo-Ortiz, A.; Thomsen, H.; Johnson, N. P.; von Hippel, P. H.; Aspuru-Guzik, A.; Marcus, A. H. “Electronic Transition Moments of 6-Methyl isoxanthoptherin (6-MI) – A Fluorescent Analog of Guanine,” Nucleic Acids Research, 2013, 41, 995 – 1004.

6. Widom, J. R.; Johnson, N. P.; von Hippel, P. H.; Marcus, A. H. “Conformation of 2-aminopurine (2-AP) dinucleotide by ultraviolet 2D fluorescence spectroscopy (UV-2D FS),” New Journal of Physics, invited research article for special issue on 2D optical coherence spectroscopy, 2013, 15, 025028-1-16.

7. Lee, W.; Jose, D.; Phelps, C.; Johnson, N. P.; von Hippel, P. H.; Marcus, A. H. “A Single-Molecule View of the Assembly Pathway, Subunit Stoichiometry and Unwinding Activity of the Bacteriophage T4 Primosome (Helicase-Primase) Complex,” (manuscript submitted February 20, 2013 to Biochemistry).