Yining Zeng received his Ph.D. under the supervision of Dr. Paul F. Barbara at the University of Texas at Austin in 2007. During his Ph.D. studies, he developed apparatus for single-molecule detection. He applied single-molecule techniques to the study of melting induced by nucleocapsid protein (NC) and annealing of HIV-1 Transactivation Response (TAR) DNA sequence. Secondary structural fluctuations as a result of NC-induced melting were limited to the terminal stems only. The mechanism for the fluctuations was complex. The annealing activity of different regions along the TAR structure was probed by short, complementary, targeted oligomers. Stable states of the putative nucleation complexes for the annealing process were kinetically trapped and investigated. This single-molecule spectroscopy method directly probed kinetic reversibility and the chaperone role of NC at various stages along the reaction sequence.
These results led to a detailed understanding of NC-chaperoned reverse annealing and partially annealed conformational substates. The annealing reaction was observed to occur through both stem and loop regions.The stem-mediated annealing dominated; it was supported by a dynamic programming computational approach developed from the thermodynamic parameters from measuring NC-induced melting. A small nucleic-acid binding molecule, argininamide, was also studied relative to its specific inhibition to annealing. The loop-mediated annealing was found to be potentially more inhibited than the stem-mediated one.
At NREL, Dr. Zeng is working on developing and applying microscopy and spectroscopy tools to investigate the cellulose structure. Non-destructive imaging with high spatial and chemical resolution will provide ultrastructure information for celluloses while under their natural condition or during biomass conversion processes. In addition to improving knowledge on the fundamentals of cellulose, the information will also help to find more efficient energy conversion pathways.
- Landes, C.; Zeng, Y.; Liu, H.; Musier-Forsyth, K.; Barbara,P. (2007). "Single Molecule Study of the Inhibition of HIV-1 Transactivation Response DNA:DNA Annealing by Argininamide." Journal of American Chemical Society (129:33); p. 10181.
- Zeng, Y.; Liu, H.; Landes, C.; .Kim, Y.; Ma, X.; Zhu, Y.; Musier-Forsyth, K.; Barbara, P. (2007). "Probing Nucleation, Reverse Annealing, and Chaperone Function along the Reaction Path of HIV-1 Single Strand Transfer." Proceedings of the National Academy of Sciences, USA (104:31); p. 12651.
- Liu, H.*; Zeng,Y.*; Landes, C.; Kim, Y.; Zhu, Y.; Ma, X.; Vo, M.; Musier-Forsyth, K.; P. Barbara, P. (2007). "New Insights on the Role of Nucleic Acid/Protein Interactions in Chaperoned Nucleic Acid Rearrangements of HIV-1 Reverse Transcription." Proceedings of the National Academy of Sciences, USA (104:13); p. 5261 (*equal contribution).