Correlating Biomolecular Experimental Measurements with Computational Simulations

Fingerprints can be generated from both experimental and simulation data.

The Science

Understanding the structural changes a biomolecule undergoes during processing is important in the design of, for example, new routes to convert biomass to biofuels. However, when studying these processes it often is difficult to correlate kinetic experiments with computer simulations. Both the experiments and the simulations provide a time-ordered understanding of the biological process at hand, but the results are often hard to compare. Research by an international consortium that includes Jeremy Smith of Oak Ridge National Laboratory has developed a new mathematical method, “Dynamical Fingerprints,” that allows researchers to visualize the essential kinetic features of an experiment and compare these features directly to computational simulation results. Structural changes present in the simulation can be assigned to experimentally observed processes. The new method enables enhanced interpretation of experiments ranging from neutron scattering to fluorescence correlation spectroscopy and Förster resonance energy transfer efficiency. Combining simulations and experiments will enable progress in areas such as biofuel production and design of advanced materials, which require a clear understanding of how molecules move and interact. The approach is applied here to a test case interpreting single molecule fluorescence correlation spectroscopy experiments on a set of fluorescent peptides with molecular dynamics simulations. The peptides exhibit complex kinetics shown to be consistent with the apparent simplicity of the experimental data. Moreover, the fingerprint approach can be used to design new experiments with site-specific labels that optimally probe specific dynamical processes in the molecule under investigation.


Noe, F., S. Doose, I. Daidone, M. Löllmann, M. Sauer, J. Chodera and J. Smith. 2011. “Dynamical Fingerprints for Probing Individual Relaxation Processes in Biomolecular Dynamics with Simulations and Kinetic Experiment,” Proceedings of the National Academy of Sciences (USA) 108(12). DOI:10.1073/pnas.1004646108.


The research was supported by DOE SciDAC funding and was just published online in the Proceedings of the National Academy of Sciences (USA).