applying royal society of chemistry cheminformatics skills to support the pharmasea project
TRANSCRIPT
![Page 1: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/1.jpg)
Applying Royal Society of Chemistry Cheminformatics Skills to Support
the PharmaSea Project
Antony Williams, Alexey Pshenichnov, Valery Tkachenko, Ken Karapetyan, David Sharpe
ACS San Francisco
August 2014
![Page 2: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/2.jpg)
Cancer Deaths Worldwide
![Page 3: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/3.jpg)
Top Treatments for Cancer
![Page 4: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/4.jpg)
• Over half of all drugs introduced between 1940 and 2006 were of natural origin or inspired by natural compounds
Importance of Natural Products
![Page 5: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/5.jpg)
Natural Products for all of us!
![Page 6: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/6.jpg)
We Are Doomed I Tell You!!!
![Page 7: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/7.jpg)
We Are Doomed I Tell You!!!
![Page 8: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/8.jpg)
The Dangers of Algal Blooms!
![Page 9: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/9.jpg)
Nature’s Little Pharmacy
O
O
O
O
O
O
O
OO
O
O
O
O
CH2CH3
OH
CH3
CH3CH3CH3
CH3
CH3
H
H
H
H
H
HH
H
H
H
HH
HH
H
![Page 10: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/10.jpg)
We Are Doomed I Tell You!!!
![Page 11: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/11.jpg)
Antibiotic resistance
![Page 12: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/12.jpg)
Discovery Curve Decay
![Page 13: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/13.jpg)
RSC and Natural Products
![Page 14: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/14.jpg)
![Page 15: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/15.jpg)
Focus on Marine Natural Products
• RSC cheminformatics support to include:• Deliver “PharmaSea website”• Provide access to natural products subset • Develop “dereplication techniques”
• Searching NMR features against database• Develop advanced searches for MS data
• Host Open Data from the PharmaSea project and make available to the community
![Page 17: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/17.jpg)
The PharmaSea Website
• RSC is open-sourcing a chemical registry system as a result of Open PHACTS
• Chemical Registry system used to underpin the PharmaSea website – behind login
• Will be enhanced with data deposition capabilities and “dereplication”
![Page 18: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/18.jpg)
The PharmaSea Website
![Page 19: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/19.jpg)
The PharmaSea Website
![Page 20: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/20.jpg)
The PharmaSea Website
![Page 21: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/21.jpg)
New Repository Architecturedoi: 10.1007/s10822-014-9784-5
![Page 22: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/22.jpg)
New Repository Architecture
Compounds Reactions Spectra Materials Documents
CompoundsAPI
ReactionsAPI
SpectraAPI
MaterialsAPI
DocumentsAPI
CompoundsWidgets
ReactionsWidgets
SpectraWidgets
MaterialsWidgets
DocumentsWidgets
Data tier
Data access tier
User interface
components tier
Analytical Laboratory application
User interface tier
(examples) Electronic Laboratory Notebook
Paid 3rd party integrations (various platforms – SharePoint, Google, etc)
Chemical Inventory application
![Page 23: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/23.jpg)
Compounds
![Page 24: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/24.jpg)
Reactions
![Page 25: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/25.jpg)
Analytical data
![Page 26: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/26.jpg)
Crystallography data
![Page 27: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/27.jpg)
Deposition of Data
![Page 28: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/28.jpg)
Extending PharmaSea Site• PharmaSea website will be extended
• Spectral data handling: Support Dereplication
![Page 29: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/29.jpg)
Identifying novel compounds
• Compounds are collected from the ocean• Extraction via chromatography• Analytical sciences including:
• UV-Vis data (Lambda-max)• Mass spectrometry (formula/mass)• NMR spectroscopy (HNMR/2D)• Utilized for dereplication,,,
![Page 30: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/30.jpg)
Is this already known or not??
![Page 31: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/31.jpg)
4 Me singlets4 Me doublets
1 OMe singlet
Aromatic protons
Identifying novel compounds
![Page 32: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/32.jpg)
Identifying novel compounds
2D NMR data will give details regarding substitutions and this information can be used in the dereplication process
![Page 33: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/33.jpg)
What we need is…
• If we could have:• A DB containing known marine natural products• This would give formula and mass for searching• The DB has all spectral data available for each
compound• If experimental data are not available then use
the compound to COMPUTE spectral features
![Page 34: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/34.jpg)
RSC Acquires Marinlit
• All Marinlit chemical compounds in ChemSpider• Marinlit developers are dereplication experts
![Page 35: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/35.jpg)
• Index literature related to marine natural products: 26K articles and growing
• Structure searchable database• Data includes taxonomy, location and literature• “Spectral features” generated algorithmically• Utilize the spectral features for dereplication
![Page 36: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/36.jpg)
![Page 37: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/37.jpg)
![Page 38: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/38.jpg)
PharmaSea Dereplication
• Work in progress:• Produce “dereplication widget” to embed in
the PharmaSea website• Generate “structure features” file for every
new compound deposited to PharmaSea• Ideal would be to utilize spectral data directly
to elucidate structures – “Computer Assisted Structure Elucidation”. ACD/Labs….
![Page 39: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/39.jpg)
CASE-based Elucidation
• Computers can elucidate structures today with greater efficiency and success than many scientists – see Patrick Wheeler’s talk
• Natural products specifically can be very challenging and CASE is well-proven
• ACD/Labs have delivered their CASE-system (ACD/Structure Eludicator) to the project
![Page 40: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/40.jpg)
1D & 2D NMR Synchronized Processing
The Software displays correlations for assigned spectra and structures, and highlights correlations that are likely to be erroneous.
![Page 41: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/41.jpg)
![Page 42: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/42.jpg)
ChemSpider supporting CASERSC delivered entire ChemSpider structure dataset for inclusion into the Structure Elucidator software.
![Page 43: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/43.jpg)
CASE vs Microscopy?DOI: 10.1002/anie.201203960
![Page 44: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/44.jpg)
Single Molecule AFM
![Page 45: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/45.jpg)
CASE vs Microscopy?DOI: 10.1002/anie.201203960
![Page 46: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/46.jpg)
Next:Tagging Natural Products
![Page 47: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/47.jpg)
Next:Tagging Natural Products
![Page 48: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/48.jpg)
Next:Tagging Natural Products
![Page 49: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/49.jpg)
Next:Tagging Natural Products
![Page 50: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/50.jpg)
Future Plans
• Roll out tagging on ChemSpider to crowdsource marine natural products subset
• Implement tagging for further details onto PharmaSea website
• Collaborate with other natural product sources • Mass spectrometry fragmentation prediction
![Page 51: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/51.jpg)
Future Plans – MS Fragmenter
![Page 52: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/52.jpg)
Future Plans – MS Fragmenter
![Page 53: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/53.jpg)
Future Plans
![Page 54: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/54.jpg)
Modern NMR Approaches To The Structure Elucidation
of Natural Products
Volume 1: Instrumentation and Software
Volume 2: Data Acquisition and Applications to Compound
Classes
Edited by Antony Williams, RSC, Gary Martin, Merck and
David Rovnyak, Bucknell University
To be published: 2015 (RSC)
![Page 55: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/55.jpg)
To be published: 2015 (Springer)
Computer-based Structure Elucidation from Spectral Data
Will include a functional demo version of the ACD/Structure Elucidator software to teach the basic approaches to computer-assisted structure elucidation
Authored by Mikhail Elyashberg, Kirill Blinov and Antony Williams
![Page 56: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/56.jpg)
Acknowledgments
• Alexey Pshenichnov, Ken Karapapetyan and Valery Tkachenko (RSC – US Cheminformatics)
• Marcel Jaspars (University of Aberdeen)• John Blunt and Murray Munro (Marinlit)• Serin Dabb (RSC, Marinlit)• Patrick Wheeler and David Hardy (ACD/Labs)
![Page 57: Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project](https://reader036.vdocument.in/reader036/viewer/2022081404/559f75801a28abfb718b47ee/html5/thumbnails/57.jpg)
Thank you
Email: [email protected]: 0000-0002-2668-4821 Twitter: @ChemConnectorPersonal Blog: www.chemconnector.com SLIDES: www.slideshare.net/AntonyWilliams