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BP: Fachverband Biologische Physik

BP 2: Protein Function

BP 2.1: Talk

Monday, March 26, 2007, 12:15–12:30, H43

Reduced Molecular Models in (Bio)molecular Design — •Kay Hamacher — Max-Planck-Institut fuer Physik komplexer Systeme, Dresden

Apoptosis regulating proteins play an essential role in the development of organisms, immune responses and other cellular mechanisms. The BCL-2 protein family contains the BH3 motif, which was found to be of crucial importance in e.g. cancer. The isolated, unstructured BH3-peptide can be modified by a hydrocarbon linkage to regain function as was recently shown in experiment [1] and act therefore as a pharmacological active molecule. We show how an effective, coarse-grained model can be parametrized (using molecular dynamics simulations as well as density-functional theory computations) to investigate the stability effects of such covalent cross-linking. We explain why the peptide dynamics is crucial for the proper function of the linker and the resulting folding properties of the peptide. Long range stabilization effects can be shown by time series analysis techniques as well as by information theory motivated measures. The resulting model [2] is suitable for rational design of generic cross-linking systems in silicio.

[1] L.D.Walensky et al. Science 305, 1466 (2004)

[2] K.Hamacher, A.Hübsch, J.A.McCammon. J. Chem. Phys. 124, 164907 (2006)