Conformational Ensembles from Experimental Data and Computer Simulations

Conformational Ensembles from Experimental Data and Computer Simulations

Poster Abstracts

106-POS Board 26 Integration of SAXS Data into Biomolecular Simulations Marie Weiel , Ines Reinartz, Alexander Schug. Karlsruhe Institute of Technology, Karlsruhe, Germany.

The cardinal aim of structural analyses in molecular biology and biophysics is to reveal an interrelation between macromolecular structure and conformational changes on the one hand and function of biological macromolecules on the other hand. Biological small angle X-ray scattering (SAXS) is an experimental technique for structural characterization of macromolecules and complementary to common high-resolution methods such as X-ray crystallography and NMR spectroscopy. To date, SAXS data are often interpreted by ambiguous reconstruction of low- resolution three-dimensional models from one-dimensional scattering intensities or assembly of rigid high-resolution elements. However, with large structural rearrangements being involved, these methods do not yield satisfying results. We include the limited information from SAXS into molecular dynamics (MD) simulations using native structure-based models (SBM). A particular initial structure, e.g. from X-ray or NMR methods, is defined as the global energetic minimum in a minimally frustrated single-basin energy landscape dominated by native interactions. The resulting description in terms of a smooth energy funnel can provide rich information about complex processes and is computationally efficient. In order to incorporate information from SAXS, a bias term is added to the SBM potential so that conformations reproducing the experimental target data are energetically favoured. In this vein, SAXS data may be reasonably interpreted whilst simultaneously retaining chemical knowledge and sampling power of molecular force fields. Running SAXS-guided MD simulations of a protein in some known initial configuration, one can obtain a well-grounded atomistic structure of the protein in another conformation corresponding to the experimental data by dynamically fitting the starting model to the SAXS intensity. Giving fast and reliable structure predictions for transiently populated conformations and related conformational changes, we hope to make a significant contribution to unraveling the relation between macromolecular structure and function.

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