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Albany 2015:Book of Abstracts

Albany 2015
Conversation 19
June 9-13 2015
©Adenine Press (2012)

The Role of Solvent Mobility in Protein Dynamics

Proteins are soft materials in which the internal motions are essential for their functions. Therefore, an understanding of protein dynamics is fundamental importance to biology. The mobility of the atoms, and further, of the atomic groups and the molecules, is temperature dependent because the temperature is a fundamental determinant of the atomic kinetic energy (Xie, Tao & Liu, 2013). It has been shown (Vitkup et al., 2000) that the temperature of the solvent, and hence its mobility, is a dominant factor in determining the atomic fluctuations of the protein above the glass transition temperature. Nevertheless, the detailed information about effects of the solvent temperatures on the protein molecular motions, conformational space sampling, and free energy landscape (FEL) of the protein-solvent system, remains unclear. Moreover, the question of how the solvent mobility dictates the hierarchical protein dynamics (Henzler-Wildman & Kern, 2007), from the low-tier group fluctuations to the high-tier collective motions of the entire protein, remains unanswered. A series of multiple, long molecular dynamics simulations (MD) were performed on the proteinase K-solvent system with the protein and solvent at different temperatures (either 300 K or 180 K, constituting four temperature combinations). Comparative analyses of the obtained trajectories demonstrate that the temperatures of the solvent, compared to the temperatures of the protein itself, have an overwhelming effect on protein dynamics, including the flexibility, mobility, molecular motions, and sampled conformational spaces of the protein. Comparison between FELs constructed from metadynamics simulations reveals that proteinase K has more conformational substates, larger conformational entropy, and lower thermostabilility at the high than at the low solvent temperatures, whereas these thermodynamic properties are independent of the protein temperatures. Comparative analyses of the total hydrogen-bonding numbers in the MD trajectories at the four combined temperatures reveal that it is the competitive hydrogen-bonding interactions (or collision) between water molecules and surface-exposed protein atoms and between atoms within the protein that transmit the solvent kinetic energy over the entire protein structure, ultimately leading to the enhanced conformational flexibility and collective motions of the protein at the high solvent temperatures. Based on the above results, it is reasonable to conclude that the solvent mobility plays a crucial role in facilitating the cascade amplification of microscopic fluctuations of atoms and atomic groups into the functionally important global collective motions of the protein.

This work is supported by NSFC (Grant Nos. 31370715 and 31160181) and the National Basic Research Program of China (2013CB127500)

References
    Henzler-Wildman, K. A. & Kern, D. (2007). Dynamic personalities of proteins. Nature 450, 964-972. Vitkup, D., Ringe, D. Petsko, G. A. & Karplus, M. (2000). Solvent mobility and the protein 'glass' transition. Nat. Struct. Biol. 7, 34-38.

    Xie, Y. H., Tao, Y. & Liu, S. Q. (2013). 153 Wonderful roles of the entropy in protein dynamics, binding and folding. J. Biomol. Struc. Dyn. 31(suppl 1), 98-100.


Qiong Yang
Peng Sang
Shu-Qun Liu*

Laboratory for Conservation and Utilization of Bio-Resources
Yunnan University
Kunming, P.R. China

Ph:* (86)871-5035257
shuqunliu@gmail.com