Investigation of Structural Stability of Etanercept in Vacuum and Aqueous Solution by Steered Molecular Dynamics Simulation
PAN Qi1, LI Dai-xi1*, GUO Bai-song2, YANG Chun-sheng2, YANG Zhi2
1. Institute of Food Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China; 2. Institute of Freeze-drying Technology, Shanghai Tofflon Science and Technology Co., Ltd., Shanghai 201108, China
Abstract��OBJECTIVE To investigate the stability of etanercept in vacuum and water to lay foundation for study on its bioactiveprotection. METHODS Umbrella sampling and steered molecular dynamics simulation aqueous solution adopted to study the dissociation process of dimer etanercept with Gromacs software and amber99sb-ildn force field. RESULTS Potential of mean forcel(PMF) free energy of etanercept dissociation in vacuum was approximately three times of that in aqueous solution. And the maximum barrier force of etanercept dissociation in vacuum was approximately ten times of that in aqueous solution. The solvation environment had effect on the stability of antibody protein. Freeze-drying in vacuum could improve the stability of antibody protein. CONCLUSION In the process of steered molecular dynamics simulation, the pulling force can be got easily and is less affected by other factors, which can be used to characterize the stability of active structure of antibody protein dimer.
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PAN Qi, LI Dai-xi, GUO Bai-song, YANG Chun-sheng, YANG Zhi. Investigation of Structural Stability of Etanercept in Vacuum and Aqueous Solution by Steered Molecular Dynamics Simulation. Chinese Pharmaceutical Journal, 2016, 51(10): 786-791.
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