Structural Bioinformatics, BIophysics, and Drug Design

		Docking Our primary focus lies on the design and implementation of novel docking algorithms for binding mode prediction and also for virtual screening.  Our current docking software BALLDock uses several heuristics like Simulated Annealing and Genetic Algorithms to search for putative binding modes in the search space of all receptor-ligand complexes. The BALLDock is implemented in C++ using our molecular modelling library BALL. We also devised several scoring functions to better estimate the free energy of binding, i.e. for protein-carbohydrate complexes, and are continuing our work in this field to devise other application-specific scoring functions. Docking methods and molecular dynamics simulations are also part of our research in Grid Computing.
		QSAR and QSPR QSAR and QSPR methods try to model biochemical properties like toxicity, drug-likeness or binding activity by using Machine Learning methods. The BALL library was equipped with several QSAR modeling methods like PLS, SVR, kNNR that allow the user to build QSAR models using BALL. Further extensions are planned to make QSAR modelling more convenient for BALL users. These methosds are being used in several cooperations with experimental groups for lead finding on numerous targets.
		Homology Modeling Homology Modelling is a concept to predict the tertiary structure of a given target sequence by using known template structures that have high sequence similarity to the target sequence. In our research we use Homology Modelling to get approximate structures of drug targets for docking and binding pocket analysis. We apply these techniques together with docking methods to the identification of possible inhibitors for various targets, e.g., kinases and glycosyl transferases. Part of this research is conducted as part of the DFG-funded SFB 766.
		Theoretical Biophysics We have long been working on the energetics and dynamics of biomolecular interactions. The interaction of proteins with water and counter ions is one of the most intriguing phenomenons in biophysics. the interactions are complex, nonlocal, and highly dynamic. It is thus little surprising that modeling solvation effects is one of the key hurdles in docking. We are working on new theoretical models to understand these interactions and are closely collaborating with experimental groups interested in studying these effects using scattering techniques.
		BALL and BALLView Over the years we have implemented numerous techniques for molecular modeling and drug design. We have made these methods available through the open-source C++ framework BALL and  BALLView.

People working in this area:

Nina Fischer, Andreas Kämper, Marc Röttig , Marcel Schumann

Selected publications:

• Kerzmann, A, Fuhrmann, J, Kohlbacher, O, and Neumann, D (2008). BALLDock/SLICK: A new Method for Protein-Carbohydrate Docking J. Chem. Inf. Model., 48(8):1616-1625.
• Peifer, C, Urich, R, Schattel, V, Abdaleh, M, Röttig, M, Kohlbacher, O, and Laufer, S (2008). Implications for selectivity of 3,4-diarylquinolinones as p38aMAP kinase inhibitors Bioorg. Med. Chem. Lett., 18(4):1431-1435.
• Andreas Hildebrandt, Ralf Blossey, Sergej Rjasanow, Oliver Kohlbacher, and Hans-Peter Lenhof (2004) Novel formulation of nonlocal electrostatics Phys. Rev. Lett., 93:108104.
• Fajun Zhang, Maximilian W Skoda, Robert M Jacobs, S. Zorn, R.A. Martin, C.M. Martin, G.F. Clark, Sophie Weggler, Andreas Hildebrandt, Oliver Kohlbacher, and Frank Schreiber (2008) Reentrant Condensation of Proteins ins Solution Induced by Multivalent Counterions Phys. Rev. Lett., 101(14):148101.
• Raub, S, Steffen, A, Kämper, A, and Marian, CM (2008). AIScore - Chemically diverse empirical scoring function employing quantum chemical binding energies of hydrogen-bonded complexes J. Chem. Inf. Model., 48(7):1492-1510.
• Kerzmann, A, Neumann, D, and Kohlbacher, O (2006). SLICK - Scoring and Energy Functions for Protein-Carbohydrate Interactions J. Chem. Inf. Model., 46:1635-1642.
• Moll, A, Hildebrandt, A, Lenhof, H, and Kohlbacher, O (2006). BALLView: A tool for research and education in molecular modeling Bioinformatics, 22(3):365–366.
• Kohlbacher, O and Lenhof, H (2000). BALL - Rapid Software Prototyping in Computational Molecular Biology Bioinformatics, 16(9,):815–824.