HOME- Bryn Mawr Conference
- Workshops & Training
- 2010 Oxford (Discovery)
- 2010 Oxford (ADMET)
- 2009 Oxford (Discovery)
- Blanchard, H
- Bryant, S
- Coveney, P
- Hardy, B
- Hawkins, P
- Klamt, A
- Knapp, S
- Kranz, M
- Liebeshuetz, J
- Oledzki, P
- Pirok, G
- Wolber, G
- Zamora, I
- Bursary Award
- 2009 Oxford (ADMET)
- 2008 Oxford
- 2006 Oxford
- Exhibition
- Registration
- Jobs
- Contact
- Support
- Schedule
|
|
|
|
|
|
|
As one of the founders of Inte:Ligand, Dr. Gerhard Wolber is heading the group for "software, technology and algorithmic science" at Inte:Ligand. After his MSc. degree in applied computer science (application area: computer-aided drug design) he finished his PhD in pharmaceutical chemistry at the University of Innsbruck. Gerhard Wolber developed the two programs "CombiGen" (ilib diverse) and "LigandScout", which are now marketed by Inte:Ligand and form the technical and scientific basis for Inte:Ligand's software and the basis for applied research carried out at Inte:Ligand and the company's customers. Several publications in the field of pharmacophore discovery show success stories in applying these methods.
His research interests include the development of algorithms for drug-receptor interaction, structure- and ligand-based virtual screening, 2D and 3D visualization techniques as well as 3D pharmacophore modeling and its use to solve biological problems.
|
|
Advanced 3D Pharmacophore Modeling and Screening Techniques to find Novel Kinase Inhibitors
Led by Gerhard Wolber (Inte:Ligand)
Virtual screening using 3D pharmacophores has been established as an important and commonly used technique for virtual screening in recent years [1-2]. Using the example of Cyclin-Dependent Kinase 2 (CDK2) we demonstrate the software tool (LigandScout), which allows for rapid and transparent development of high-quality 3D pharmacophore. Besides the easy and automated creation of pharmacophore models from protein/ligand complexes, LigandScout provides intuitive pharmacophore overlay and interpolation work-flows based on a robust and fast chemical-feature-based alignment algorithm. The underlying methods are scientifically published [3-4] and based on several years of experience in pharmacophore creation, and support for various common pharmacophore formats like the export to Catalyst(tm), MOE(tm) or Phase(tm) which allow interoperability to screening platforms from other vendors. The full-featured 3D graphical user interface makes the exploration of the active site and pharmacophore creation within the complex efficient and transparent. Binding site analysis, pharmacophore-based alignment and the creation of shared feature pharmacophores are designed to make the drug discovery workflow more efficient. In this half-day workshop we will demonstrate how to derive structure- and ligand-based pharmacophores using the LigandScout modelling environment. The individually developed pharmacophores will be validated against sets of active and inactive molecules for CDK2 and subsequently used for virtual screening in multi-conformational libraries to detect novel compounds with CDK2 activity. The group will subsequently apply similar approaches to derive their own pharmacophores for case study problems.
References
[1] Langer T., Hoffmann R. D. Pharmacophores and Pharmacophore Searches; VCH/Wiley, Methods and Principles in Medicinal Chemistry, Vol. 32, R. Mannhold, H. Kubinyi, G. Folkers, series editors, ISBN: 3527312501 (2006)
[2] Wolber G., Seidel T., Bendix, F., Langer T. Molecule-pharmacophore superpositioning and pattern matching in computational drug design.Drug Discov Today. 2008 Jan ;13 (1 2):23-9
[3] Wolber, G.; Dornhofer, A. A.; Langer, T.; Efficient overlay of small organic molecules using 3D pharmacophores J. Comput. Aided Mol. Des.; 2007; 20(12); 773-788.
[4] Wolber, G.; Langer, T.; LigandScout: 3-D Pharmacophores Derived from Protein-Bound Ligands and Their Use as Virtual Screening Filters. J. Chem. Inf. Model; 2005; 45(1); 160-169.
|
|
|
|
|
|
|
|
|
