Protonation state and free energy calculation of HIV-1 protease–inhibitor complex based on electrostatic polarisation effect |
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Authors: | Maoyou Yang Xiaonan Jiang |
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Institution: | 1. School of Science, Qilu University of Technology, Jinan 250353, China;2. Department of Fundamental Education, Shandong College of Arts, Jinan 250014, China |
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Abstract: | The protonation states of catalytic Asp25/25′ residues remarkably affect the binding mechanism of the HIV-1 protease–inhibitor complex. Here we report a molecular dynamics simulation study, which includes electrostatic polarisation effect, to investigate the influence of Asp25/25′ protonation states upon the binding free energy of the HIV-1 protease and a C2-symmetric inhibitor. Good agreements are obtained on inhibitor structure, hydrogen bond network, and binding free energy between our theoretical calculations and the experimental data. The calculations show that the Asp25 residue is deprotonated, and the Asp25′ residue is protonated. Our results reveal that the Asp25/25′ residues can have different protonation states when binding to different inhibitors although the protease and the inhibitors have the same symmetry. This study offers some insights into understanding the protonation state of HIV-1 protease–inhibitor complex, which could be helpful in designing new inhibitor molecules. |
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Keywords: | protonation state binding free energy HIV-1 protease electrostatic polarisation effect |
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