Conformational Ensembles from Experimental Data and Computer Simulations

Conformational Ensembles from Experimental Data and Computer Simulations

Saturday Speaker Abstracts

Dynamics of Proteins Under Crowded Conditions in Simulations and Experiments Michael Feig 1,2 , Grzegorz Nawrocki 1 , Po-hung Wang 4 , Isseki Yu 4 , Takanori Kigawa 2,3 , Yuji Sugita 2,4 . 1 Michigan State University, East Lansing, MI, USA, 2 RIKEN, Kobe, Japan, 3 RIKEN, Yokohama, Japan, 4 RIKEN, 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.

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