个人简介

Camille and Henry Dreyfus Teacher-Scholar Grant

研究领域

Physical and Biophysical Chemistry

The long-term objective of our research is to elucidate the molecular recognition mechanisms used by proteins to control biomineralization processes. A variety of interesting proteins that are found in mineralized tissues act as nature's crystal engineers, where they control the growth of inorganic composites such as hydroxyapatite (HAP) (the mineral phase found in bone/teeth). A particularly important class of acidic proteins found in hard tissues is known to regulate normal hard tissue formation and remodeling, and they are also involved in pathological processes such as dental caries, kidney stone formation and arterial calcification. However, due to the difficulties in studying the protein structure and function at inorganic solid surfaces, there is still remarkably little known of the molecular structure-function relationships governing hard tissue engineering. Our group has been developing and applying solid-state NMR (ssNMR) techniques to determine protein structure and dynamics on their biologically relevant hydroxyapatite surface. These studies have led us to the beginnings of a high-resolution model for the acidic salivary protein statherin. Statherin N-terminal Interaction with HAP Our goal for the next few years is to test and develop using NMR and molecular modeling a full three-dimensional statherin structure that connects the molecular mechanisms underlying hydroxyapatite adsorption thermodynamics and crystal engineering function. This research involves collaborations with the groups of UW faculty members David Castner (Chemical Engineering), Patrick Stayton (Bioengineering), and Charles Campbell (Chemistry). Another long-standing research interest is the study of the role played by dynamics in protein-nucleic acid recognition. Our objective is to probe nucleic acid dynamics through the conjoint use of solution and solid-state deuterium NMR. By exploiting the synergy between the two methods, we have measured internal motions quantitatively enough and with sufficient coverage of motional time scales to begin to correlate motions with function. Problems of current interest include how motion affects recognition of a DNA dodecamer containing the recognition site for the Hha I methyltransferase, the interaction between HIV TAR and Tat peptide constructs, and how motion affects recognition in human U1A protein, a paradigm for highly specific RNA-protein interactions. This research involves a collaboration with the group of Gabriele Varani (UW Chemistry and Biochemistry)

近期论文

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"13C-19F and 15N-19F Intermolecular REDOR NMR Study of the Interaction of TAR RNA with Tat Peptides" Wei Huang, Gabriele Varani and Gary P. Drobny, J. Am. Chem. Soc., 2010, 132 (50), 17643. "Toward a Structure Determination Method for Biomineral-Associated Protein Using Combined Solid- State NMR and Computational Structure Prediction" David Masica, Jason Ash, Moise Ndao, Gary Drobny, Jeffrey Gray, Structure 2010 18:12, 1678. "A Slow Exchange Theory of Non-Rigid Rotation in TAR RNA" P. Emani, D.C. Echodu, G. Olsen, G. Varani, G.P. Drobny, J. Phys. Chem. B 2010 114: 48, 15991. "A Sum Frequency Generation and Solid-State NMR Study Peptide Structure, Orientation and Dynamics of Polystyrene-adsorbed Peptides" Tobias Weidner, Nicholas F. Breen, Kun Li, Gary Drobny, David Castner, PNAS 2010 107(30), 13289. "A 13C{31P} REDOR Study of the Role of Basic Amino Acids in Protein-Hydroxyapatite Surface Recognition" Moise Ndao , Jason Ash, P. S. Stayton, & G.P. Drobny, Surface Science 2010 604 :15-16, L39-L42. "Unifying Solution and Solid-State NMR Studies of Nucleic Acid Dynamics" Kari Pederson, Prashant Emani, Dorothy Echodu, Greg Olsen, Michael Bardaro, Zahra Shajani, Paul Miller, Gary Meints, Gabriele Varani, Gary P. Drobny, Encyclopedia of NMR (posted on-line) 2010. "Atomic Motions of RNA in Space and Time" G.L. Olsen, M. Barbardo, D. Echodu, G. Drobny, G. Varani, J. Amer. Chem. Soc. 2009 132 (1) 303. "Hydration Dependent Dynamics in TAR RNA" G.L. Olsen, M. Barbardo, D. Echodu, G. Drobny, G. Varani, J Biomol NMR 2009 45:133-142. "Amide or Amine: Determining the Origin of the 3300 cm-1 NH Mode in Protein SFG Spectra Using 15N Isotope Labels" Tobias Weidner, Nicholas F. Breen, Gary P. Drobny, David G. Castner, J. Phys. Chem. B 2009, 113, 15423. "A Solid-State Deuterium NMR and Sum-Frequency Generation Study of the Side-Chain Dynamics of Peptides Adsorbed onto Surfaces" N. F. Breen, T. Weidner, K. Li, D. G. Castner, and G. P. Drobny, J. Am. Chem. Soc. 2009 131, 14148. "A 13C{31P} REDOR NMR Investigation of the Role of Glutamic Acid Residues in Statherin-Hydroxyapatite Recognition" M. Ndao, J. T. Ash, N. F. Breen, P. S. Stayton, and G. P. Drobny, Langmuir 2009, 25, 12136. "A Nanofluoro Nucleoside as a Sensitive 19F-NMR Probe of Nucleic Acid Conformation" Nivrutti B. Barhate1, Rekha N. Barhate1, Pavol Cekan2, Gary Drobny1 and Snorri Th. Sigurdsson Org. Lett. 2008 10(13), 2745. "A Comparative Study of Funaose Ring Dynamics in the HhaI Binding Site by Solution and Solid State NMR" D.C. Echodu, Z. Shajani, K. Pedersen, Jr., G. Varani, G.P. Drobny J. Phys. Chem.B 2008, 112 (44), 13934. "Dynamics of the Phosphodiester Backbone in the HhaI Binding Site" K. Pedersen, G. A. Meints, Z. Shajani, P. Miller & G. P. Drobny, J.Amer Chem Soc. 2008 130, 9072. "Dynamics of the Furanose Rings in the HhaI Binding Site" G. A. Meints, P. Miller, K. Pedersen, Z. Shajani, & G. P. Drobny, J.Amer. Chem. Soc. 2008 130, 7305. "Solid State Deuterium NMR Studies of HIV-1 TAR RNA Reveal Motions on the Micro-second-Nanosecond Time Scale" G. Olsen, D.C. Echodu, Z. Shajani, M.F. Bardaro, Jr., G. Varani, G.P. Drobny, J. Amer. Chem. Soc. 2008 130 (10), 2896. "Assembly of alpha-helical peptide coatings on hydrophobic surfaces.", J.R. Long, N. Oyler, G.P. Drobny, P.S. Stayton, J. Amer. Chem. Soc., 124 6297 (2002). Click here to download a reprint of this article "Structure and Dynamics of Hydrated Statherin on Hydroxyapatite via Solid State NMR.", J. R. Long, W. J. Shaw, P. S. Stayton, and G. P. Drobny, Biochemistry (accelerated publication), 40 15451 (2001). Click here to download a reprint of this article "Dynamic impact of methylation at the M. HhaI target site: A Solid state deuterium NMR study.", G.A. Meints & G.P. Drobny, Biochemistry, 40 12436 (2001). Click here to download a reprint of this article "Modeling Furanose Ring Dynamics in DNA.", G. A. Meints, T. Karlsson and G.P. Drobny, J. Amer. Chem. Soc., 123 10030 (2001). "A solid state NMR study of dynamics in a hydrated salivary peptide adsorbed to hydroxyapatite.", W. J. Shaw, J. R. Long, P. S. Stayton, and G. P. Drobny, J. Amer. Chem. Soc., 122 7118 (2000).