Conformational Ensembles from Experimental Data and Computer Simulations

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Conformational Ensembles from Experimental Data
and Computer Simulations Poster Abstracts
85
50-POS Board 10
Rotamer Libraries for Spin and Fluorescence Labels Aid Structural Interpretation of
Experimental Data
Daniel Klose1 , Svetlana Kucher2, Heinz-Juergen Steinhoff2, Gunnar Jeschke1.
1ETH Zurich, Zurich, Switzerland, 2University 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.