Conformational Ensembles from Experimental Data and Computer Simulations

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Conformational Ensembles from Experimental Data
and Computer Simulations Saturday Speaker Abstracts
14
Dynamics of Proteins Under Crowded Conditions in Simulations and Experiments
Michael Feig1,2, Grzegorz Nawrocki 1, Po-hung Wang4, Isseki Yu4, Takanori Kigawa2,3, Yuji
Sugita 2,4.
1Michigan State University, East Lansing, MI, USA, 2RIKEN, Kobe, Japan, 3RIKEN,
Yokohama, Japan, 4RIKEN, Wako, Japan.
Crowding in cellular environments results in constant non-specific interactions between
macromolecules impacting their stability and dynamics. Altered dynamics involves both retarded
diffusional motions and altered conformational sampling as a result of crowding. An analysis of
computer simulations of crowded protein solutions ranging from homogeneous solutions of
small model proteins such as villin to large cytoplasmic models is presented and compared to
experimental data, primarily from NMR spectroscopy. The integration of simulation and
experiment offers new insights into the transient weak associations of proteins under crowded
conditions that result in reduced translational and rotational diffusion rates and the possibility of
expanding the native-state conformational ensemble under dilute conditions towards non-native
states. The comparison between simulations and experiment also offers an opportunity to
critically evaluate the ability of current force fields to accurately capture the interactions of
proteins under realistic cellular conditions.