Integration of Computer Simulation and Neutron Scattering in the Characterization of Protein Dynamics

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Protein function often requires large-scale motion of functionally-important domains. Few techniques are available that can directly probe protein motions. Among the most direct is molecular dynamics simulation in which, using an empirical potential energy function, the equations of motion of a system of atoms are solved numerically. In this way detailed descriptions of protein dynamics can be built up for timescales up to about 100 ns. Integration of molecular dynamics simulations and neutron scattering provide insights of process in the proteins in the atomic details. An exciting new development in the experimental detection of functionally-important domain motions in proteins is the application of neutron spin-echo spectroscopy (NSE). Spin echo directly probes coherent (i.e., pair correlated) scattering on the 10-100 ns timescale. Recent work has demonstrated that domain motions in the tetrameric protein Alcohol Dehydrogenase (yADH) can be positively identified and characterized with this technique. Inspired by these results, we conducted theoretical calculations of the coherent time correlated neutron scattering from all-atomic molecular dynamics simulations data of the same protein. NSE allows the direct measurement of the intermediate scattering function and this way allows the direct comparison between simulation and experiment. The global translational and rotational diffusional components were decomposed and the internal dynamics of these functional domains characterized. The translational, rotational, and the internal effective diffusion constants were determined from the intermediate scattering function and the results compared with the NSE data.