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Effects of ligand binding on the mechanical stability of protein GB1 studied by steered molecular dynamics simulation

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Abstract

Regulation of the mechanical properties of proteins plays an important role in many biological processes, and sheds light on the design of biomaterials comprised of protein. At present, strategies to regulate protein mechanical stability focus mainly on direct modulation of the force-bearing region of the protein. Interestingly, the mechanical stability of GB1 can be significantly enhanced by the binding of Fc fragments of human IgG antibody, where the binding site is distant from the force-bearing region of the protein. The mechanism of this long-range allosteric control of protein mechanics is still elusive. In this work, the impact of ligand binding on the mechanical stability of GB1 was investigated using steered molecular dynamics simulation, and a mechanism underlying the enhanced protein mechanical stability is proposed. We found that the external force causes deformation of both force-bearing region and ligand binding site. In other words, there is a long-range coupling between these two regions. The binding of ligand restricts the distortion of the binding site and reduces the deformation of the force-bearing region through a long-range allosteric communication, which thus improves the overall mechanical stability of the protein. The simulation results are very consistent with previous experimental observations. Our studies thus provide atomic-level insights into the mechanical unfolding process of GB1, and explain the impact of ligand binding on the mechanical properties of the protein through long-range allosteric regulation, which should facilitate effective modulation of protein mechanical properties.

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Acknowledgments

This work was supported in part by grants from the National Natural Science Foundation of China (11204267, 21473207, 31171267), National Basic Research Program of China (973 program No. 2013CB933704), Natural Science Foundation of Hebei Province (A2014203126), Program for the Top Young Talents of Hebei Province, and the Beijing Municipal Education Commission (KM201310005030).

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Authors and Affiliations

  1. College of Science, Yanshan University, Qinhuangdao, 066004, China

    Ji-Guo Su & Shu-Xin Zhao

  2. CAS Key Lab for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Science, Beijing, 100049, China

    Xiao-Feng Wang & Jing-Yuan Li

  3. College of Life Science and Bioengineering, Beijing University of Technology, Beijing, 100024, China

    Chun-Hua Li

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  1. Ji-Guo Su
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  2. Shu-Xin Zhao
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Correspondence to Chun-Hua Li or Jing-Yuan Li.

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Su, JG., Zhao, SX., Wang, XF. et al. Effects of ligand binding on the mechanical stability of protein GB1 studied by steered molecular dynamics simulation. J Mol Model 22, 188 (2016). https://doi.org/10.1007/s00894-016-3052-7

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  • DOI: https://doi.org/10.1007/s00894-016-3052-7

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