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Oral presentation | Open | Published:

Coarse-grained molecular models for high-throughput and multi-scale functional investigations

In this contribution we discuss the development, implementation, and the subsequent application of in silico, coarse-grained molecular models. The proposed approach allows for bridging a methodological gap between sequence-based bioinformatics and molecular dynamics simulations: molecular interactions can be modeled based on physio-chemical model in a highly parallelizable and high-throughput-ready fashion.

We demonstrate the broad applicability of such an approach by discussing the assembly of the bacterial ribosome [1] and potential points of interference by antibiotica, HIV protease [2] and its evolutionary dynamics en route to drug resistance [3]. These methodologies were further applied to a signaling cascade in leukemia [4, 5] and can be used for design by e.g. global optimization techniques [6]. In addition we show recent results on further computational improvements and additional observations from a physicist's/chemist's point of view.

References

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    Hamacher K, Trylska J, McCammon JA: Dependency Map of Proteins in the Small Ribosomal Subunit. PLoS Comput Biol. 2006, 2: e10-10.1371/journal.pcbi.0020010.

  2. 2.

    Hamacher K, McCammon JA: Computing the Amino Acid Specificity of Fluctuations in Biomolecular Systems. J Chem Theo Comp. 2006, 2: 873-10.1021/ct050247s.

  3. 3.

    Hamacher K: Gene. 2007, submitted

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    Hamacher K, Hübsch A, McCammon JA: A minimal model for stabilization of biomolecules by hydrocarbon cross-linking. J Chem Phys. 2006, 124: 164907-164914. 10.1063/1.2185645.

  5. 5.

    Hamacher K: Information Theoretical Measures to Analyze Trajectories in Rational Molecular Design. J Comp Chem. 2007, 28: 2576-2580. 10.1002/jcc.20759.

  6. 6.

    Hamacher K: Adaptation in Stochastic Tunneling Global Optimization of Complex Potential Energy Landscapes. Europhys Lett. 2006, 74: 944-950. 10.1209/epl/i2006-10058-0.

  7. 7.

    Hamacher K: Energy landscape paving as a perfect optimization approach under detrended fluctuation analysis. Physica A. 2007, 378: 307-314. 10.1016/j.physa.2006.11.071.

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Correspondence to Kay Hamacher.

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Keywords

  • Leukemia
  • Molecular Dynamic
  • Molecular Dynamic Simulation
  • Dynamic Simulation
  • Global Optimization