| CROSS-DISCIPLINARY PHYSICS AND RELATED AREAS OF SCIENCE AND TECHNOLOGY |
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Allosteric Mechanism of Calmodulin Revealed by Targeted Molecular Dynamics Simulation |
| Qian-Yun Liang†, Chun-Li Pang†, Jun-Wei Li, Su-Hua Zhang, Hui Liu, Yong Zhan**, Hai-Long An** |
Key Laboratory of Molecular Biophysics of Hebei Province, Institute of Biophysics, School of Sciences, Hebei University of Technology, Tianjin 300401
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Qian-Yun Liang, Chun-Li Pang, Jun-Wei Li et al 2017 Chin. Phys. Lett. 34 068701 |
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Abstract Calmodulin (CaM) is involved in the regulation of a variety of cellular signaling pathways. To accomplish its physiological functions, CaM binds with Ca$^{2+}$ at its EF-hand Ca$^{2+}$ binding sites which induce the conformational switching of CaM. However, the molecular mechanism by which Ca$^{2+}$ binds with CaM and induces conformational switching is still obscure. Here we combine molecular dynamics with targeted molecular dynamics simulation and achieve the state-transition pathway of CaM. Our data show that Ca$^{2+}$ binding speeds up the conformational transition of CaM by weakening the interactions which stabilize the closed state. It spends about 6.5 ns and 5.25 ns for transition from closed state to open state for apo and holo CaM, respectively. Regarding the contribution of two EF-hands, our data indicate that the first EF-hand triggers the conformational transition and is followed by the second one. We determine that there are two interaction networks which contribute to stabilize the closed and open states, respectively.
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Received: 22 November 2016
Published: 23 May 2017
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| Fund: Supported by the Natural Science Fund for Distinguished Young Scholars of Hebei Province under Grant Nos C2015202340 and C2013202244, the Fund for Outstanding Talents of Hebei Province under Grant No C201400305, the National Natural Science Fund of China under Grant Nos 11247010, 11175055, 11475053, 11347017, 31600594, 31400711 and 11647121, the Fund for the Science and Technology Program of Higher Education Institutions of Hebei Province under Grant No QN2016113,???the Scientific Innovation Grant for Excellent Young Scientists of Hebei University of Technology under Grant No 2015010, and the Natural Science Foundation of Hebei Province under Grant No C2017202208. |
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