Mykola Dimura wins at the Biophysical Society Meeting in New Orleans, USA, the Poster Award of Fluorescence Subgroup.
Titel: Multi-conformation Biomolecular Structure Determination by High-precision FRET and Molecular Simulations
Abstract:
A comprehensive methodology study for FRET-restrained modeling of biomolecules is presented. Conformations of three-state model protein (Atlastin) are determined based on synthetic FRET data in the given example. The demonstration covers five steps including:
- NMSim[3][4] geometric simulations for extensive sampling of the conformational space using only information about one of the three states.
- Experiment planning for determining efficient labeling positions and distance pairs for FRET measurements based on proposed ensemble of possibilities generated by NMSim.
- FRET-screening[1] for assessing an arbitrary set of conformations (from MD trajectories, crystal structures etc.) with respect to their agreement with FRET measurements[2].
- FRET-guided NMSim simulation tool for assembling structural units with high precision and determining the confidence levels of the generated models.
- Precission and accuracy assessment and quality control.
Using these tools, formerly unknown conformations of various biomolecules were determined[5]. An example on T4 Lysozyme with 24 FRET restraints will be presented.
[1] www.mpc.hhu.de/software/fps.html
[2] Sindbert S, Kalinin S et al. (2006) Accurate Distance Determination of Nucleic Acids via Forster Resonance Energy Transfer: Implications of Dye Linker Length and Rigidity. J. Am. Chem. Soc., XXX: Vol., pp. 2463-2480.
[3] Krüger D. M., Aqeel A., and Gohlke H. (2012) NMSim web server: Integrated approach for normal mode-based geometric simulations of biologically relevant conformational transitions in proteins. Nucl. Acids Res., 40, pp. W310-W316.
[4] cpclab.uni-duesseldorf.de/nmsim
[5] Kalinin S., Peulen T, Sindbert S et al. (2012) A toolkit and benchmark study for FRET-restrained high-precision structural modeling. Nat Methods 9, 1218-1225.