SOMA2 – Drug Design Environment

Drug design environment – SOMA2

The SOMA2 project 2002-2006• Tekes (National Technology Agency of Finland) DRUG2000 program.

• Organizes and updates CSC’s (the Finnish IT Center for Science) modeling program environment to meet the standards in modern computer-aided molecular design.

• Promotes the use of computing tools in drug discovery research work in Finland.

• Provides easy access to computational tools through WWW – interface.

• Integrates different tools, operates as middleware program.

• Allows user to define unique computational workflow (pipeline, network etc.).

Software for ADME and structure-based drug discovery• Databases of chemistry and protein structures and tools to analyze them• Docking and classification of molecules• QSAR (Quantitative Structural Analysis Research)• Computer-assisted high-throughput screening

Design of ligands• ADME predictions (Absorption, Distribution, Metabolism and Excretion), Toxicity• Data management, data mining and visualization

O

O

H

H H

H

FROM MOLECULES … … TO PROTEINS … …AND CELL-LEVEL ACTIVITIES

Drug design environment – SOMA2

Query database

ISIS on Solaris

Calculate chemical properties

Sybyl on Linux

Convert to 3D

Corina on Solaris

Dock to target protein

GOLD on Linux

INTERNET,researcher’s PC

Scientist interface,SOMA2 environment

CSC-network andcomputing grid

SOMA2 environment O

O

2D > 3Dconversion

ADMEprediction Docking

• 2D structure,• 3D structure,• original data,• docking score,• ADME-values

O

O

O

O

2D structure,known data

INPUT:

OUTPUT:

CML

XML XML XML

a)

b)

Drug design environment – SOMA2

Basic technical concept• WWW – interface is based on the XML –

description of a program.

• Different machine architectures are hidden.

• Automatic generation of program and platform specific configuration files.

• CML (chemical markup language) is used as internal data format (data transferred in XML).

• Unique computational workflows.

Drug design environment – SOMA2

Model workflow

Figure from:

Lehtovuori, P. Nyrönen, T., SOMA - Workflow for Small Molecule Property Calculations on a Multiplatform Computing Grid, J. Chem. Inf. Model., 2006, 46(2), 620-625.

Drug design environment – SOMA2

Generic user interface generation• User interface generated from description that is based on XML schema (“template”).

• No programming skills required to produce XML – description of a program.

• New programs are easily added to SOMA2 – environment.

• Save expert user knowledge in XML.

Flexibility• Not only for cheminformatics and drug design.

• SOMA2 – system can be applied in almost every application area.

Open source thinking• Similar products available usually they are commercial.

• Although some of the programs used are commercial, SOMA2 system is planned to be open source.

Drug design environment – SOMA2

Model workflows• User can choose a

predefined workflow for specific task.

• Predefined workflow can still be freely modified.

• Possibility to save own workflows as a template.

Drug design environment – SOMA2

Input molecules• Upload files from local

computer.

• Sketch molecules within the user interface.

Drug design environment – SOMA2

Database query• MDL ISIS host

databases.

• Support for structure search.

• Search results imported to SOMA2 – system or downloaded.

Drug design environment – SOMA2

Program configuration• Easy configuration of

programs.

• Useful help texts and reasonable defaults included in program XML.

• System includes model templates for running a program.

Drug design environment – SOMA2

Workflow manager• Free navigation

between steps.

• Insert, change and delete operation supported.

Result view• Spreadsheet like

result view.

• Tools for sorting and filtering data.

• Basic data analysis.

• Save molecular data in different formats.

Drug design environment – SOMA2

Drug design environment – SOMA2

Result details• Visualisation of the

result molecules.

• Summary of computed properties.

Additional information

CSC – the Finnish IT Center for Science• http://www.csc.fi

SOMA2 – project:• http://www.csc.fi/proj/drug2000/index.phtml.en

Acknowledgements

Tekes (National Technology Agency of Finland):• http://www.tekes.fi

ChemAxon Ltd.:• http://www.chemaxon.com