The Promise and the Reality of Turning Chemical Literature into

Information

Tom DomanChicago ACS – Wiggins Symposium

3/25/2007

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.

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

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

Natural Products Discussed in Danishefsky Paper (p. 540)

Can Cheminformatics / Molecular Modeling Shed Some Light on 3D Similarity of These Compounds?

1. Retrieve structures (preferably from public / free sources)

2. Convert to 3D (if necessary)3. Generate conformers4. Perform 3D similarity / pharmacophore

analysis

The Desired Transformation

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

Google“tricycloillicinone”

• 89 hits• None seem to lead to structure in

electronic form

Wikipedia:“acetylsalicylic acid”

Wikipedia

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

PubChem

PubChem

• Only 1 name / subname found:– Jiadifenin

emolecules.com“Dup-697”

emolecules.com

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

DNP on the Web

DNP on the Web

• Entries found for:– Tricycloillicinone– Jiadifenin

• Registration for Free Trial

SciFinder

• Structures found for all compounds except NGA0187

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

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

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 2D3D problem ends up being pretty complicated!