The FMP has developed a database of commercially available compounds which is used to design our in-house HTS collection and is additionally applied to create focused libraries. But the dramatically increase of unique compounds of one order of magnitude from less than 10 to around 30 to 40 million compounds currently and approximately hundred million compounds in the next years requires a reorganization and redevelopment of our storage and searching strategy. To manage such a massive amount of data we developed a Registration Database for registration and normalisation of vendor catalogues. This database contains the highly redundant data of the vendor catalogues and is converted in a second step into the non-redundant Unique Structure Database which represents a data warehouse combining vendor data, structural descriptors and in-house classification tools including our earlier developed ADMET- and reactivity filters as well as our in-house fragment-based fingerprints used for library design tasks. The management of both database systems is part of a new developed Java application, which handles the user management for the data upload in the Registration Database and the conversion into the Unique Structure Database. Further a first version of a Web service is in preparation. This service allows the scientist not only to search for compounds and fragments in the Unique Structure Database but also to combine such a search with the FMP tools to classify compounds for their usability in biological assays.
EUGM 2013 - Bernd Rupp (FMP) Chemical Information systems: From compound collections to rationally designed HTS library
1. LEIBNIZ-INSTITUT FÜR MOLEKULARE PHARMAKOLOGIE
BERND RUPP
Chemical Information systems:
From compound collections to rationally
designed HTS library
2. LEIBNIZ-INSTITUT FÜR MOLEKULARE PHARMAKOLOGIE
The Library Design Team
Head: Ronald Kühne
Module Cheminformatic/Drug Design
M. Lisurek
Design and enhancement of
Screening- Libraries
Maintenance of Vendor-Data
- Library Design:
Design of focussed Libraries
Design of Virtual Screens
Design of Docking Studies
Development of Homology Models
- Modelling:
Pharmacophore Models
QSAR
Module Database Design and IT
M. Pawletta, R. AL-Yamori and B. Rupp
- Database design:
Development and Maintenance of relational
Database of Screening results
Development of commercial available
compound library
- Software development
- Hardware Management
Tools for Processing Structural Data
3. LEIBNIZ-INSTITUT FÜR MOLEKULARE PHARMAKOLOGIE
Screening Libraries @ FMP
[CBB 6: - 1.280 Cpds, LOPAC-library of
pharmacologically active annotated Cpds]
2005 CBB 1: - 16.544 Cpds from ChemDiv
2006/07 CBB 4: - 4.224 Cpds, ArtChem-library
CBB 3: - 4.576 Cpds, fragment library
2008/09 CBB 2: - 3.520 Cpds from Enamine, IBS,
ChemDiv, KeyOrganics, Maybridge
2011 CBB X: - 1.765 Cpds from IBS
2012 CBB Y: - 2.600 Cpds from Enamine
and UORSY
[CBB 5: - 1.780 Cpds synthesized by academic
groups, collected by E. Specker]
∑ ~35.000 Cpds
€ 130.000
€ ~10.000
€ ~30.000
€ ~80.000
€ ~45.000
€ ~45.000
€ 20.000
∑ € ~360.000
4. LEIBNIZ-INSTITUT FÜR MOLEKULARE PHARMAKOLOGIE
Database of Available Chemical Substances (DACS)
Usage:
- Experimental:
design of HTS, Ligation,
Building Block und focused
Libraries
- Theoretical:
Virtual Screening, Docking
Testing new Methods
Advantages:
- Effective Data Control
- Individual Tagging and Search
functionality
18. LEIBNIZ-INSTITUT FÜR MOLEKULARE PHARMAKOLOGIE
Unique structure database
- Standardization of chemical Structures
- Normalization of the Data (removal of
redundancy)
- Storage in a Data Warehouse system
21. LEIBNIZ-INSTITUT FÜR MOLEKULARE PHARMAKOLOGIE
Outlook
Web interface and start of the Webserver
Implementation of FMP Reactivity
and Tox. Tag
Implementation of FMP Solubility
Prediction and other in-house models
Development of a GUI for UDB Routine
Connection to other Public recourses like
PubChem and ChEMBL
Development of virtual Screening and
Docking interfaces
Update and Bug fix for SDF-Registration
and UDB-Routine
Further Targets:
Coming Soon:
22. LEIBNIZ-INSTITUT FÜR MOLEKULARE PHARMAKOLOGIE
Acknowledgment
Drug Design / Molecular Modeling
• Ronald Kühne, Dr.
• Daniela Müller, Dr.
• Kirill Piotukh, Dr.
• Martyna Pawletta , master student
• Raed Al-Yamori, tech. Informatics
• Robert Opitz, Dr. student
• Matthias Barone, Dr. student
• Matthias Müller, Dr. student
• Michael Lisurek, Dr.
• Frank Eisenmenger, Dr.
Screnning Unit/ Compound
Managment
• Jens-Peter von Kries, Dr.
• Martin Neuenschwander, Dr.
• Edgar Specker, Dr.
Former member:
• Jörg Wichard, Dr. (Bayer AG)
• Lara Kuhnke , master student
Funding:
• Helmholtz Drug Research
initiative; Ronald Frank, Dr.
Partner:
• Prof. Gerhard Wolber (FU Berlin)
• Chemaxon