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Curriculum Vitae

Tanya M. Raschke

Contact

Stanford University Department of Structural Biology Fairchild Building, Room D-100 Stanford, CA 94305-5126 Tel: 650-725-0754 FAX: 650-723-8464 raschke@stanford.edu

Education and Training

	September 2004 to present		Department of Structural Biology Stanford University School of Medicine Life Sciences Research Associate with Professor Michael Levitt
	September 1999 to August 2004		Department of Structural Biology Stanford University School of Medicine Postdoctoral fellow with Professor Michael Levitt Investigating the hydrophobic effect with molecular simulation and protein structure prediction
	May 1999 Ph.D.		Department of Molecular and Cell Biology University of California, Berkeley Doctoral Research with Professor Susan Marqusee Folding of ribonuclease H from Escherichia coli: the role of a partially folded, kinetic intermediate
	May 1993 B.S. Biochemistry (with honors)		Department of Molecular and Cell Biology Pennsylvania State University Undergraduate Research with Professor Kenneth Johnson The fluorescent labeling of the kinesin head domain to monitor microtubule binding and release

Research Experience

Postdoctoral Research

i) Hydration of small, hydrophobic solutes using molecular dynamics simulations

The spatial density and orientation of water molecules in dilute solutions of benzene and cyclohexane were measured using a gridding technique. Water molecules show a strong tendency to hydrogen bond with the faces of the benzene ring. Water molecules occur at high density along the edge of the benzene ring and around cyclohexane, and show a preference for a tangential orientation. Measurement of the hydrogen bonding within and between hydration shells shows enhanced structure within shell 1 and shell 2, and decreased structure between shell 1 and shell 2.

ii) Modeling hydrophobic collapse using molecular dynamics simulations

Molecular dynamics simulations of simple, hydrophobic solutes in water show cooperative collapse into aggregates. The energy of formation of these clusters, as well as details of the solvent structure can be determined from the trajectories. These energetics correspond very well to experimentally determined solute transfer free energies, and we are using these data to investigate the basis of the hydrophobic effect.

iii) Protein structure prediction

Three-dimensional structures of proteins with no detectable sequence homology to proteins with known structures can be predicted. Our method involves generating many potential structural "decoys" for each sequence. The conformational space that is sampled is comprised of structural fragments found in existing protein structures. The best predicted structure is selected from the decoy set using clustering, evaluation of potential energy functions, and visual inspection. We participated in a community-wide, double-blind prediction experiment (CASP5) and placed within the top 10 groups in the New Fold category.

iv) Database of predicted protein structures from Shewanella oneidensis

Sequences from the genome that have significant sequence homology to known protein structures were predicted using a threading technique. These predicted structures and their related alignments have been placed in a web-accessible database for use in further investigations of this organism, which shows promise in bioremediation applications. http://gollum.stanford.edu/shewa/

Graduate Research

i) Identification of a folding intermediate of ribonuclease H

Rapid mixing techniques were used to identify a transient kinetic folding intermediate. The structured regions of the intermediate were determined using hydrogen exchange and heteronuclear NMR. This intermediate consists of a structured core region of the protein which resembles both the acid molten globule and partially folded forms detected under native conditions. These studies showed that folding of ribonuclease H is a hierarchical process where the most stable regions of the native state fold first.

ii) Assessing the role of the kinetic intermediate in folding

Several mutant ribonucleases H were constructed, and their stability and folding kinetics were evaluated using a global fit of the denaturant-dependent data. Mutations in the folding core destabilize both the native and intermediate states and decrease the rate of folding, consistent with the obligatory intermediate model.

Undergraduate Research

Biophysical studies of the kinesin head domain

Fluorescent labeling of free cysteines of the Drosophila kinesin head domain was used to evaluate the binding and release of microtubules.

Awards and Honors

Damon Runyon Cancer Research Foundation Postdoctoral Fellowship (1999-2002) National Science Foundation Predoctoral Fellowship (1993-1996) University of California Regents Fellowship (1997-1998) Outstanding Graduate Student Instructor Award (1997) Barry M. Goldwater Scholarship (1991-1993) Penn State University Scholar Magna cum laude , Penn State University

Teaching Experience

	Resource Person International Workshop on Pattern Discovery in Biology Covenant University, Ota, Ogun State, Nigeria April 18-27, 2005
	Teaching Assistant Dept. of Structural Biology, Stanford University SB228: Computational Structural Biology
	Graduate Student Instructor Dept. of Molecular and Cell Biololgy, U.C. Berkeley MCB111: Structural Biology MCB110L: Biochemistry Laboratory

Publications

1. Raschke TM , Levitt M. Nonpolar solutes enhance water structure within hydration shells, while reducing interactions between them. Proceedings of the National Academy of Sciences of the United States of America (2005). 102:6777-6782. [PDF]


2. Raschke TM , Levitt M. Detailed hydration maps of benzene and cyclohexane reveal distinct water structures. Journal of Physical Chemistry B (2004) 108:13492-13500. [PDF]


3. Raschke TM , Tsai J, Levitt M. Quantification of the hydrophobic interaction by simulations of the aggregation of small hydrophobic solutes in water. Proceedings of the National Academy of Sciences of the United States of America (2001) 98:5965-5969. [PDF]


4. Wedekind JE, Trame CB, Dorywalska M, Koehl P, Raschke TM , McKee M, FitzGerald D, Collier RJ, McKay DB. Refined crystallographic structure of Pseudomonas aeruginosa exotoxin A and its implications for the molecular mechanism of toxicity. Journal of Molecular Biology (2001) 314:823-837. [PDF]


5. Raschke, TM , Kho J and Marqusee S. Confirmation of the hierarchical folding of RNase H: a protein engineering study. Nature Structural Biology (1999) 6:825-831. [PDF]


6. Raschke, TM and Marqusee, S. Hydrogen exchange studies of protein structure. Current Opinion in Biotechnology (1998) 9:80-86. [PDF]


7. Raschke, TM and Marqusee, S. The kinetic folding intermediate of ribonuclease H resembles the acid molten globule and partially unfolded molecules detected under native conditions. Nature Structural Biology (1997) 4:298-304. [PDF]


8. Goedken, ER, Raschke, T. and Marqusee, S. Importance of the C-terminal helix to the stability and enzymatic activity of Escherichia coli ribonuclease H. Biochemistry (1997) 36:7256-7263. [PDF]