1 / 21

The Promise and the Reality of Turning Chemical Literature into Information

The Promise and the Reality of Turning Chemical Literature into Information. Tom Doman Chicago ACS – Wiggins Symposium 3/25/2007. Abstract.

obert
Download Presentation

The Promise and the Reality of Turning Chemical Literature into Information

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. The Promise and the Reality of Turning Chemical Literature into Information Tom Doman Chicago ACS – Wiggins Symposium 3/25/2007

  2. Abstract • The fields of computational chemistry and especially chemical informatics have advanced greatly in recent years, and vastly more sophisticated analyses of chemical results are possible these days. However, due to technical, business, and political realities, there are still significant barriers to conducting these analyses in a timely fashion. Using a recent case study, I will highlight the challenges in turning traditional 2D chemical graphs found in many chemistry-related publications into 3D molecular models.

  3. Opportunities Provided by Gary Wiggins: • Indiana University School of Informatics, IUPUI: Informatics 572 – Computational Chemistry and Molecular Modeling • External Advisor – NIH funded Exploratory Center for Cheminformatics Research at IU • Helpful conduit for communication & collaboration between Lilly & IU

  4. Acc. Chem. Res. 2006, 39, 539-549.

  5. Natural Products Discussed in Danishefsky Paper (p. 540)

  6. Can Cheminformatics / Molecular Modeling Shed Some Light on 3D Similarity of These Compounds? • Retrieve structures (preferably from public / free sources) • Convert to 3D (if necessary) • Generate conformers • Perform 3D similarity / pharmacophore analysis

  7. The Desired Transformation

  8. Easy, Right? • Google • Wikipedia • PubChem • emolecules • DNP on the Web • SciFinder • Corina • WebLab ViewerLite • Catalyst

  9. Google“tricycloillicinone” • 89 hits • None seem to lead to structure in electronic form

  10. Wikipedia:“acetylsalicylic acid”

  11. Wikipedia • No entries found for any of the 7: • Tricycloillicinone • Merrilactone A • Jiadifenin • Scabronine G • Garsubellin A • 11-O-Debenzoyltashironin • NGA0187

  12. PubChem

  13. PubChem • Only 1 name / subname found: • Jiadifenin

  14. emolecules.com“Dup-697”

  15. emolecules.com • Alas, no entries for any of the 7 names (or carefully chosen snippets of them)

  16. DNP on the Web

  17. DNP on the Web • Entries found for: • Tricycloillicinone • Jiadifenin • Registration for Free Trial

  18. SciFinder • Structures found for all compounds except NGA0187

  19. Further Processing • SMILES generated, but Corina failed on 4 • So, from SciFinder, viewed in WebLab ViewerLite & converted to MOL files • Imported as is to Accelrys “Catalyst” • No conformational model could be built for Jiadifenin, but others okay • Many HipHop (common features) models built, shown on next slide is from: • Garsubellin A, Merrilactone A, Scabronine G • Permitted: • 0-5 HBA • 0-5 Hydrophobic • 0-5 Hydrophobic Aliphatic

  20. Potentially Interesting Overlay of Garsubellin A (yellow) & Scabronine G (white)

  21. Conclusions • Chemical structure still sometimes hard to obtain from open sources. • Natural product stereochemistry may stymie computational tools. • Manuscripts typically don’t embody live structures (but wait, it’s 2007!); here must return to carefully curated structure. • A simple 2D3D problem ends up being pretty complicated!

More Related