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Evidence for a New Theory of Allostery Andrew Michaelson Northeastern University

Evidence for a New Theory of Allostery Andrew Michaelson Northeastern University Professor Mary Jo Ondrechen. Why Do We Want to Do This?. New Drugs Design of new sites Design of new effectors

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Evidence for a New Theory of Allostery Andrew Michaelson Northeastern University

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  1. Evidence for a New Theory of Allostery Andrew Michaelson Northeastern University Professor Mary Jo Ondrechen

  2. Why Do We Want to Do This? • New Drugs • Design of new sites • Design of new effectors • (Understanding allosteric effects may be lead us to design allosteric sites and effectors for non-allosteric enzymes)

  3. Current Theory of Allostery • Concerted Model • Sequential Model

  4. A Classic Example

  5. Uracil Phosphribosyltransferase • What does it do? • Why is this important?

  6. Methods • THEMATICS • PropKa • Motif

  7. Uracil Phosphoribosyltransferase(Inactive Form)

  8. Uracil Phosphoribosyltransferase(Active Form)

  9. But Are They Different?(0.679 Angstroms)

  10. Uracil Phosphoribosyltransferase(Inactive Form)

  11. Uracil Phosphoribosyltransferase(Active Form)

  12. And How Are They Different?(1.743 Angstroms)

  13. Results

  14. Results

  15. Results

  16. Analysis

  17. Results

  18. Analysis

  19. Conclusions

  20. Acknowledgments • I would like to thank Professor Ondrechen • I would like to thank the Ondrechen Group. • I would like to thank all the other people working on the Allostery project as well.

  21. References • 1. YASARA Biosciences (2007) YASARA: Yet another scientific artificial reality application. Available: http://www.yasara.org/. Accessed 13 April 2010. • 2. Bioinformatics-Biostatistics & Computational Biology Greece. YASARA the absolute structure viewer. Triantafillos Paparountas. Available: http://bio-informatics.gr/content/view/45/26/ . Accessed 12 March 2010.

  22. 3. Mary Jo Ondrechen, James G. Clifton, Dagmar Ringe, (2001) THEMATICS: A simple computational predictor of enzyme function from structure, PNAS. 4. 1XTU. F.C.Bernstein, T.F.Koetzle, G.J.Williams, E.E.Meyer Jr., M.D.Brice, J.R.Rodgers, O.Kennard, T.Shimanouchi, M.Tasumi, "The Protein Data Bank: A Computer-based Archival File For Macromolecular Structures," J. of. Mol. Biol., 112 (1977): 535. References

  23. 5. 1XTT. F.C.Bernstein, T.F.Koetzle, G.J.Williams, E.E.Meyer Jr., M.D.Brice, J.R.Rodgers, O.Kennard, T.Shimanouchi, M.Tasumi, "The Protein Data Bank: 6. Hui Li, Andrew D. Robertson, and Jan H. Jensen "Very Fast Empirical Prediction and Interpretation of Protein pKa Values" Proteins, 2005, 61, 704-721. References

  24. References 7. Delphine C. Bas, David M. Rogers, and Jan H. Jensen "Very Fast Prediction and Rationalization of pKa Values for Protein-Ligand Complexes" Proteins, 2008, 73, 765-783. 8. Freeman and Company L Stryer, WH "Biochemistry Fifth Edition" - New York, 1995

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