Chemical Biology Specialty Area at U of M

1. Chemical Biology Specialty Area at U of M Our program emphasizes highly interdisciplinary research and training, aimed at the development and integration of modern chemical methods in order to understand biological problems at the molecular level.

2. Chemical Biology Specialty Area at U of M 19 Faculty Highly Interdisciplinary Research NIH Chemistry and Biology Interface Training Grant (CBITG) Chemical Biology Colloquium Laboratory Rotation Program

3. CBITG Areas of Training Bioorganic Chemistry Nucleic Acid Chemistry Med Chem Biocatalysis & Biomolecular Design Metallobiochemistry Chemistry BMBB Microbiology Single Cell/ Molecule Studies Engineering Metabolic Pathways

4. Chemical Biology Coursework at U of M • Flexible program • Mechanisms of Chemical Reactions • Introduction to Chemical Biology • Chemical Biology of Enzymes • Nucleic Acids • Biochemistry • Optional courses (2)

5. Introduction to Graduate Research: Chem 8025 Course Objective Broaden exposure of students to new areas of chemistry by giving them practical hands-on exposure to graduate research in a participating faculty’s lab Course Description Rotate through two different laboratories. Each rotation lasts approximately seven weeks, with one credit earned for each rotation

6. Research Areas Represented among Chemical Biology Faculty at U of M • Bioanalytical & Biomaterials • Computational Chemistry • Design & Synthesis • Enzyme Chemistry • Structure & Spectroscopy • Nucleic Acids

7. Bioanalytical & Biomaterials

8. Edgar Arriaga • Michael Bowser • Marian Stankovich • Andrew Taton

9. 1.2 1.0 0.8 Fluorescence (V) 0.6 0.4 0.2 100 150 200 250 Migration Time (s) Subcellular distribution Doxorubicin Metabolites Arriaga Group, 2005 http://www.chem.umn.edu/ groups/arriaga/

10. Bowser Group Research Interestshttp://www.chem.umn.edu/groups/bowser/ APTAMERS NEUROSCIENCE • 10-Second In Vivo Monitoring • Novel Neuromessengers • Stroke • Sensory Response • New Sampling Methods • Single Neuron Analysis • Alternative Selection Methods • (CE-SELEX) • Microfluidics • Catalytic Aptamers • Aptamer Assays (neuropeptides, bacteria, etc.)

11. ~15 nm http://www.chem.umn.edu/groups/taton/ Taton Group Research:Connecting Nanotech and Biotech Application Example: Nanoparticle labels for electrophoretic analysis of DNA Challenge: How to combine nano- objects and biological molecules? (Electron microscope image of polymer-coated nanoparticles) DNA bands are visible with the naked eye. No staining necessary. (cuvette of DNA-modified, polymer-coated nanoparticles)

12. Computational Chemistry

13. Christopher Cramer (*) • Jiali Gao • William Gleason • Donald Truhlar • Rick Wagner • Darrin York

14. Jiali Gao http://www.chem.umn.edu/groups/gao • Computational Biology • dynamics, pathways, and catalysis • protein-membrane interactions • macromolecular assembly • Approach • combined QM/MM methods • MOVB • Monte Carlo and molecular dynamics

15. Bill Gleason - Chemical Biology Interests • Biomolecular recognition (e.g. heparin/protein interactions, receptor kinases) • Biomaterials - synthesis and properties of novel polymeric biomaterials • Biomarker discovery for clinical applications Mohammaddi Structure FGF:Receptor:Heparin 2:2:2 http://ccgb.umn.edu/~bgleason/

16. Truhlar Research Group CA H CD http://comp.chem.umn.edu/truhlar/

17. Density-functional calculations of biological reaction models York Group: Density-functional theory and hybrid QM/MM methods Hybrid QM/MM simulations of reactions in RNA and in solution http://riesling.chem.umn.edu/

18. Design & Synthesis

19. George Barany • Mark Distefano • Craig Forsyth • Larry Que • Bill Tolman • Rick Wagner

20. What do Laundry, Poker, and Proteins have in common?

21. Folding

22. GB1 A SYNTHETIC CHEMIST LOOKS AT PROTEIN FOLDING Prof. George Barany www.chem.umn.edu/groups/baranygp/index.htm

23. Distefano Research GroupOrganic and Protein Chemistry • Cancer • Catalysis • Antibiotics • Tissue Engineering http://www.chem.umn.edu/groups/distefano/

24. Forsyth Research Group PP1 - Okadaic Acid Docking Model V. A. Frydrychoski K. A. Plummer

25. Wagner Research Group Interests Drug Design and Delivery Biocatalysis C-69 H-107 Chemical Biology D-122 -Antivirals -Antitumor -Carcinogen Activating Enzymes Nanobiotechnology -Chemical Control of Protein Macrocyclization

26. Enzyme Chemistry

27. Mark Distefano • Craig Forsyth • Jiali Gao • John Lipscomb • Karin Musier-Forsyth • Larry Que

28. Species-specific differences in tRNA and amino acid recognition • Expanding the genetic code:Incorporation of unnatural amino acids • Amino acid editing/proofreading http://www.chem.umn.edu/groups/musier-forsyth/

29. Larry Que:Spectroscopic studies of oxygen activating iron enzymes with a 2-His-1-carboxylate motif • Enzymes catalyze hydrocarbon oxidations and antibiotic synthesis, degrade aromatic pollutants in soil, and sense hypoxia in cells • Spectroscopic methods used include EPR, NMR, Raman and EXAFS. Rapid kinetics techniques are used to trap reactive intermediates http://bioinorg.chem.umn.edu/quespace/

30. Structure & Spectroscopy

31. John Lipscomb • Karin Musier-Forsyth • Larry Que • Gianluigi Veglia

32. Veglia Research Group NMR Spectroscopy Molecular Modeling Enzyme Structure and Function Membrane Proteins Protein-Protein Interactions http://www.chem.umn.edu/groups/veglia/

33. NMR Studies of Membrane Proteins.Veglia Group Solution NMR Solid-state NMR

34. Nucleic Acids

35. Victor Bloomfield • Michael Bowser • Karin Musier-Forsyth • Andrew Taton • Darrin York

36. Solid-Phase RNA/DNA Synthesizer

37. Musier-Forsyth • Human tRNALys primer selection • RNA chaperone activity of HIV nucleocapsid protein http://www.chem.umn.edu/groups/musier-forsyth/

38. York Group: Multi-scale Quantum Models for RNA catalysis External potential of solute and solvent Stochastic boundary Reaction Region QM active site + MM surrounding (Newtonian dynamics) Buffer Region (Langevin dynamics) http://riesling.chem.umn.edu/

39. Summary & Conclusions Chemical Biology: represents the “happening” interface for 21st century research Come to University of Minnesota, and help put the fun into “structure & function”! http://www.chem.umn.edu/bio/