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DEEDS Super-meeting!

DEEDS Super-meeting!. Quantum Chemistry Use Case: Examining Vibrational Theory of Receptor Protein Activation. G Protein Coupled Receptors:. What are they, and why should we care?. Serotonin-Protein Therapeutic Applications. Antidepressants Antipsychotics Anorectics

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DEEDS Super-meeting!

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  1. DEEDS Super-meeting! Quantum Chemistry Use Case: Examining Vibrational Theory of Receptor Protein Activation

  2. G Protein Coupled Receptors: What are they, and why should we care? Serotonin-Protein Therapeutic Applications • Antidepressants • Antipsychotics • Anorectics • Antiemetics • Gastroprokinetics • Antimigraine Agents • Hallucinogen • Entactogens Palczewski et al. Science 289, 739-745 2000 Rosenbaum et al. Science 318, 1266-1273 2007

  3. Experimental Evidence Hara J (1977). "Olfactory discrimination between glycine and deuterated glycine by fish".Experientia33 (5): 618: 1977 Havens and Melone"The application of deuterated sex pheromone mimics of the American cockroach (Periplanetaamericana, L.), to the study of wright's vibrational theory of olfaction". Dev. Food. Sci.37 (1): 497: 1995 Franco  "Molecular vibration-sensing component in Drosophila melanogaster olfaction". Proceedings of the National Academy of Sciences of the USA108 (9): 3797: 2011 Acetophenone Haffenden "Investigation of vibrational theory of olfaction with variously labelled benzaldehydes". Food Chem.73 (1): 67: 2001 Acetophenone Turin "Molecular vibration-sensing component in human olfaction." PLoS ONE 8, e55780: 2013 "Putting a smell theory to the sniff test", Renee Twombly; Rockefeller Scientist, March 26, 2004

  4. Preliminary Concept

  5. IETS Model 1 2 Standing Wave Solutions 1 Tunneling Wave Solutions 2

  6. IETS Model e Ze 1 2

  7. A Matter of Scale (not to scale)

  8. Sample Set for 5-HT2A 5-HT2A DOX Class 2C-X Class X X

  9. Subset Tests of 5-HT2A agonists

  10. Subset Tests of 5-HT2A agonists

  11. Subset Tests of 5-HT1A agonists Ipsapirone Eptapirone Ipsapirone Zalospirone Zalospirone Newman-Tancredi et al European J. Pharmacology 355, 245: 1998 Potency Umesspirone Buspirone Buspirone Tandospirone Gepirone Alnespirone Tandospirone Prospirone Buspirone Zalospirone Ipsapirone Tandospirone De Boer et al JPET 288, 1125: 1999 Giral et al Biol Psychiatry 23, 237: 1988

  12. Proposed Experiment

  13. Classes • Case designations came naturally from the classes of proteins involved. • Due to these groups being internally comparable with respect to pharmacological activity. • Spans types of activity (agonist/antagonist) and Receptor Classes

  14. Instances in Class MDL 106907 Olanzapine Risperidone LY-367 265

  15. Types of Files

  16. Graphical Data

  17. Data Storage CSVs

  18. Future Concerns • NMR – utilize limited Gaussian NMR information to graphically replicate the NMR plots • Expand Post-processor to Scan runs – individual mol flies for each step. Tracking vital quantities (energies, thermodynamics) with respect to scanned parameter • Graphically represent atomic charge comparisons (Mullikan, NBO…) • Determine which quantities may be relevant for cross-comparison • Data Set 2.0 – heavy on scanned parameters • Data Set 3.0 (?) basis set/method comparison

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