www.digitalchemistry.co.uk

Dr. Matthew WrightProduct Director

Torus

Molecule and Markush Structure Analysis within Oracle

Digital Chemistry

• Company, formed Mid-2005• Acquired Barnard Chemical Information

(BCI) September 2005. – All previous BCI directors and staff are now

employed by Digital Chemistry.

• Aim to build on top of existing BCI technology and know-how, predominantly their Markush and Clustering methods

• Now moving into patent space

Digital Chemistry

• Product range covering – Cluster/diversity analysis– Markush library analysis– Chemical fingerprinting and dictionaries– Structure query conversion (MDL > Daylight)

• Software distributed as – Toolkits (C, C++, Java, Perl, Python)– Web Services– Application suites

Torus overview

• Torus:Server– Oracle based cartridge which integrates both Molecule

and Markush structure storage and retrieval– SQL based interface, but Query can be supplied from

SMARTS, ISIS/Draw or ChemDraw– Client may be Torus:View or any SQL supporting

application, e.g. PipeLine Pilot or customer developed system due to open nature of SQL interface

• Torus:View – Optional client for Torus:Server. Allows searching of

Torus:Server database with graphical display of results.

Markush Structures

• Presently within Torus:Server Markush structures have attachments defined in a number of ways (with unlimited members), including :

Simple substitution :

Nested R-Groups :

Bridged R-Groups :

R1

*Br

*ClR1=

R1

*Cl

*BrR2=

*O

R2 *N

R2R1=

R1

R2

* 'O

* '' * 'N

* ''R1 + R2 =

Torus: Server Function summary #1

Torus:Server supports a number of SQL based functions:

• Structural equivalence check– Are two libraries/molecules equivalent

• Sub-structure/Exact-structure searching– Into Mol and Markush

• Overlap between Markush libraries– Also produce third Markush representing overlap

• Similarity– Of molecule into Markush and between two Markush libraries

• Property calculation, both in molecule and Markush– Supports all Lipinski rules, e.g. weight, LogP etc

Torus: Server Function summary #2

Torus:Server supports a number of SQL based functions:

• Markush enumeration– Typical enumeration speeds > 100k structures per second

• Query format conversion– MDL MOL/SKC to Daylight SMARTS

• Miscellaneous utility functions

Markush Structures – current work

• Currently support substituent variation (s-variation) – useful for combinatorial chemistry

• Current and future work extends the Markush representation to cover further generalisations leading to a full Markush structure search for use in Patent systems:– Substituent variation (s-variation)

• R1 can have a number of substitutions

– Frequency variation (f-variation)• (CH2) repeats m times

– Position variation (p-variation)• R2 has a number of attachment points

– Homology variation (h-variation)• R3 is Alkyl, Methyl

R1

R3

(CH2)m

R2

H

Torus:Patent prototype demo

• Live demonstration based up Thomson patent data, all data held on laptop

• Schema contains patent PDF, patent ID and patent Markush structures

• Database covers 8,709,704,764,382,349 specific compounds if enumerated

• Oracle/Torus:Patent server running on laptop

Query creation

• Queries against Torus:Patent database are easily drawn in ISIS/Draw (supporting all ISIS Query features) and transferred back into Torus:View ready for query against the patent database in Torus:Patent

Result viewing

• Results of the query show patent structure along with the original patent in PDF format in a list

Result viewing

• Patent chemistry structures can also be displayed. A viewer is available which allows easy viewing of all Markush core/R-Group members

Tree view of Markush structure

Markush core(s)

R-Group members

Result viewing

• The original PDF of each result patent can be viewed directly from Torus:View

Contact Us

www.digitalchemistry.co.uk

info@digitalchemistry.co.uk

+44 (0)113 2181850

The Iron Shed, Harewood House Estate,Leeds, LS17 9LF, United Kingdom