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- 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
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Andreas Klamt studied physics in Göttingen and received his diploma degree in 1984 in theoretical metal physics. Then he moved on to the Max-Planck-Institut for Metal Research in Stuttgart, where he received his PhD in 1987 with a thesis on 'States of small positively charged particles in metals'.
After his PhD he directly started to work at Bayer AG in Leverkusen in the area of Computational Chemistry. Being involved in many different projects ranging from environmental distribution modelling, NMR-shift prediction, and chiral separation to drug design, he specialized on solvation and physical property calculation and developed the methods COSMO and COSMO-RS which meanwhile are widely used in the computational chemistry community. After being head of the central department for Computational Chemistry at Bayer for 3 years, he left Bayer in 1999 and founded COSMOlogic GmbH&Co.KG, Leverkusen, a company for Computational Chemistry and Fluid Phase Thermodynamics, Software and Consulting.
Since 2005 Andreas Klamt also is associate professor at the institute of Physical and Theoretical Chemistry at the University of Regensburg and teaches block courses on solvation modelling and physical property predictions in solution.
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Simulation of Drugs in Bio-membranes and Micelles
Andreas Klamt (COSMOlogic)
The calculation of membrane partition coefficients for solutes in a micelle or a biomembrane, is now possible using a novel quantum chemistry and statistical mechanics approach. Packaged as an easy to use software tool, COSMOmic [1] approximates self assembled structures such as bio-membranes or micelles as inhomogeneous layered liquids with a different polarity composition in each layer. Solute molecules in such micellar systems are treated similarly to the COSMO-RS method (see below) but, by the inhomogeneous composition of the matrix their free energy becomes dependent on the position and orientation. By sampling all relevant positions, orientations, and conformation it enables the calculation of the distribution and of free energy profiles of solutes in biomembranes and other self-assembled structures in a much more efficient, and most likely at least as rigorous and more accurate way than the standard force-field based simulation techniques. For biomembranes the free energy profiles can be converted into membrane permeabilities, applying standard assumptions. Application examples of this novel COSMOmic software for the partition coefficients and free energy barriers of solutes in bio-membranes and micelles will be demonstrated.
COSMO-RS [2] is a quantum-chemically based method for the prediction of thermodynamic properties of pure and mixed homogeneous fluids. COSMO-RS calculates the thermodynamic data from molecular surface polarities, which result from DFT calculations of the individual components of the mixture. The different interactions of molecules in a liquid, i.e. electrostatic interactions, hydrogen bonding, and hydrophobic interactions are represented as functionals of surface polarities of the partners. Using a rigorous and efficient statistical thermodynamics method for such pair-wise surface interactions, COSMO-RS finally converts the molecular polarity information into standard thermodynamic data of fluids, i.e. vapor pressures, activity coefficients, excess properties, etc. COSMO-RS meanwhile is widely validated and accepted for the predictive exploration of fluid phase thermodynamics.
References
[1] COSMOmic: A Mechanistic Approach to the Calculation of Membrane−Water Partition Coefficients and Internal Distributions within Membranes and Micelles,
Andreas Klamt, Uwe Huniar, Simon Spycher and Jörg Keldenich, J. Phys. Chem. B, 2008, 112 (38), pp 12148–12157
[2] COSMO-RS: From Quantum Chemistry to Fluid Phase Equilibria and Drug Design, A. Klamt, Elsevier, 2005
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Fig. 1: Solute molecules considered on the background of the layered biomembrane (schematic)
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