[ Research Interests ] [ Representative Publications ]

David E. Draper Professor Department of Chemistry Adjunct Professor Department of Biology Ph.D. University of Oregon Postdoctoral University of Colorado

Department of Chemistry Johns Hopkins University 3400 North Charles Street Baltimore, MD 21218-2685 U.S.A. Office Telephone: Lab Telephone: Department Fax: Email: 410.516.7448 410.516.7447 410.516.5213 draper@jhu.edu Remsen Hall Office Remsen 154

Research Interests “RNA folding” has become a vigorous area of research as many unexpected and important functional roles have been discovered for RNA molecules. My lab is using a variety of physical techniques to ask questions about fundamental principles of RNA folding energetics. Much of our work in recent years has been concerned with electrostatic aspects of RNA. Folding of an RNA tertiary structure is opposed by the unfavorable free energy needed to bring negatively charged phosphates into proximity, and it has long been known that Mg(2+) is much more effective than monovalent ions at reducing the electrostatic free energy of RNA tertiary folds. We have developed a theoretical framework which successfully accounts for the special properties of Mg(2+), and have also developed the thermodynamic background and experimental methods for measuring the overall free energy of Mg(2+) - RNA interactions. The agreement between theory and experiment so far is gratifying, though we continue to explore RNA systems that might require more sophisticated theoretical developments. Several aspects of RNA folding occupy the lab at present. One problem which has emerged from the Mg(2+) - RNA studies is the nature of the ensemble of RNA structures (containing both helical and single stranded segments) from which tertiary folding takes place. We are using a combination of molecular modeling, computation, and experiment to approach this problem. We are also asking how changes in hydration- of both ions and the RNA surface- might influence RNA stability, using calorimetry and other experimental methods. As part of these efforts to understand ions and hydration, we are working with a theoretical group to explore the behavior of monovalent ions close to RNA surfaces, where ion hydration, ion size, and specific chelation sites become important factors in the overall ion-RNA interaction energetics. Another areas of interest is the dependence of RNA stability on osmolytes, small organic molecules that cells use (along with ions) to regulate their water content in response to changes in the composition of the external medium. Virtually all osmolytes destabilize RNA secondary structure but many stabilize RNA tertiary structure. Part of the motivation for these studies is our interest in the in vivo stabilities of functional RNAs, but we also find that osmolytes can be useful tools for probing the interactions of RNAs with water and ions. Representative Publications Lambert, D., and Draper, D. E. 2007. Effects of Osmolytes on RNA Secondary and Tertiary Structure Stabilities and RNA-Mg(2+) Interactions, J Mol Biol 370: 993-1005. Grilley, D., Misra, V., Caliskan, G., and Draper, D. E. 2007. The importance of partially unfolded conformations for Mg(2+) -induced folding of RNA tertiary structure: structural models and free energies of Mg(2+) interactions. Biochemistry, 46:10266-10278. Soto, A. M., Misra, V., and Draper, D. E. 2007. Tertiary structure of an RNA pseudoknot is stabilized by "diffuse" Mg(2+) ions. Biochemistry 46: 2973-83. Lee, D., Walsh, J. D., Yu, P., Markus, M. A., Choli-Papadopoulou, T., Schwieters, C. D., Krueger, S., Draper, D. E., and Wang, Y. X. 2007. The Structure of Free L11 and Functional Dynamics of L11 in Free, L11-rRNA(58 nt) Binary and L11-rRNA(58 nt)-thiostrepton Ternary Complexes. J Mol Biol 36: 1007-22. Grilley, D., A.M. Soto, and D.E. Draper. 2006. Mg2+ - RNA interaction free energies and their relation to the folding of RNA tertiary structures. Proc. Natl. Acad. Sci. USA 103:14003-14008. Maeder, C., and D.E. Draper. 2006. Optimization of a ribosomal structural domain by natural selection. Biochemistry 45:6635-6643. Maeder, C., and D.E. Draper. 2005. A small protein unique to bacteria organizes rRNA tertiary structure over an extensive region of the 50S ribosomal subunit. J. Mol. Biol. 354:436-446. Bausch, S.L., E. Poliakova and D.E. Draper. 2005. Interactions of the N-terminal domain of ribosomal protein L11 with thiostrepton and rRNA. J. Biol. Chem. 280:29956-29963. Dunstan, M.S., D. Guhathakurta, D.E. Draper and G.L. Conn. 2005. Coevolution of protein and RNA structures within a highly conserved ribosomal domain. Chem. Biol. 12:201-206. Draper, D.E., D. Grilley and A.M. Soto. 2005. Ions and RNA folding. Annu. Rev. Biophys. Biomol. Struct. 34:221-43. Draper, D.E. 2004. A guide to ions and RNA structure. RNA 10:335-343. Misra, V.K., R. Shiman and D.E. Draper. 2003. A thermodynamic framework for the magnesium-dependent folding of RNA. Biopolymers 69:118-136. García-García, C., and D.E. Draper. 2003. Electrostatic interactions in a peptide-RNA complex. J. Mol. Biol. 311:75-88. Conn, G. L., A.G. Gittis, E.E. Lattman, V. Misra and D.E. Draper. 2002. A compact RNA tertiary structure contains a buried backbone - K+ complex. J. Mol. Biol. 318:963-973. Misra, V., and D.E. Draper. 2002. The linkage between magnesium binding and RNA folding. J. Mol. Biol. 317:509-523. Conn, G.L., D.E. Draper, E.E. Lattman and A.G. Gittis. 1999. Crystal structure of a conserved ribosomal protein - RNA complex. Science 284:1171-1174. Draper, D.E. 1999. Themes in RNA-protein recognition. J. Mol. Biol. 293:255-270.

Johns Hopkins University
3400 N. Charles St.
Baltimore, MD 21218

E-mail updates to the CMDB Webmaster