1 / 18

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

natalieh
Download Presentation

DEEDS Super-meeting!

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  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

More Related