Conformational Ensembles from Experimental Data and Computer Simulations

Conformational Ensembles from Experimental Data and Computer Simulations

Poster Abstracts

50-POS Board 10 Rotamer Libraries for Spin and Fluorescence Labels Aid Structural Interpretation of Experimental Data Daniel Klose 1 , Svetlana Kucher 2 , Heinz-Juergen Steinhoff 2 , Gunnar Jeschke 1 . 1 ETH Zurich, Zurich, Switzerland, 2 University of Osnabrueck, Osnabrueck, Germany. In structural biology, the conformation of biomolecular complexes can be investigated by techniques that require covalent modification of protein side chains or nucleotides with labels, such as spin or fluorescence labels. The interpretation of such experimental data generally benefits from taking the label’s spatial distribution into account. We previously established rotamer libraries for nitroxide spin labels, such as MTSSL, as a rapid approach that yielded good agreement with experimental data with only 0.2 nm standard deviation. Here, we extended this approach to significantly larger labels comprising up to eleven dihedral angles as found in fluorescence labels as well as in recently developed spin labels. We applied Monte Carlo sampling to efficiently generate large ensembles of label conformations, followed by clustering into a significantly smaller, yet representative, set of conformations, a rotamer library. These pre-computed libraries can be used to calculate the spatial distribution of a label within seconds on a desktop computer and thereby facilitate the comparison of experimental data to atomic structures, even for screening large ensembles or for refinement of structural models.

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