The impact of interior dielectric constant and entropic change on HIV-1 complex binding free energy prediction
At present, the calculated binding free energy obtained using the molecular mechanics/Poisson-Boltzmann (Generalized-Born) surface area (MM/PB(GB)SA) method is overestimated due to the lack of knowledge of suitable interior dielectric constants in the simulation on the interaction of Human Immunodef...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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AIP Publishing LLC and ACA
2018-11-01
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| Series: | Structural Dynamics |
| Online Access: | http://dx.doi.org/10.1063/1.5058172 |
| _version_ | 1811285469095264256 |
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| author | Yuchen Li Yalong Cong Guoqiang Feng Susu Zhong John Z. H. Zhang Huiyong Sun Lili Duan |
| author_facet | Yuchen Li Yalong Cong Guoqiang Feng Susu Zhong John Z. H. Zhang Huiyong Sun Lili Duan |
| author_sort | Yuchen Li |
| collection | DOAJ |
| description | At present, the calculated binding free energy obtained using the molecular mechanics/Poisson-Boltzmann (Generalized-Born) surface area (MM/PB(GB)SA) method is overestimated due to the lack of knowledge of suitable interior dielectric constants in the simulation on the interaction of Human Immunodeficiency Virus (HIV-1) protease systems with inhibitors. Therefore, the impact of different values of the interior dielectric constant and the entropic contribution when using the MM/PB(GB)SA method to calculate the binding free energy was systemically evaluated. Our results show that the use of higher interior dielectric constants (1.4–2.0) can clearly improve the predictive accuracy of the MM/PBSA and MM/GBSA methods, and computational errors are significantly reduced by including the effects of electronic polarization and using a new highly efficient interaction entropy (IE) method to calculate the entropic contribution. The suitable range for the interior dielectric constant is 1.4–1.6 for the MM/PBSA method; within this range, the correlation coefficient fluctuates around 0.84, and the mean absolute error fluctuates around 2 kcal/mol. Similarly, an interior dielectric constant of 1.8–2.0 produces a correlation coefficient of approximately 0.76 when using the MM/GBSA method. In addition, the entropic contribution of each individual residue was further calculated using the IE method to predict hot-spot residues, and the detailed binding mechanisms underlying the interactions of the HIV-1 protease, its inhibitors, and bridging water molecules were investigated. In this study, the use of a higher interior dielectric constant and the IE method can improve the calculation accuracy of the HIV-1 system. |
| first_indexed | 2024-04-13T02:45:29Z |
| format | Article |
| id | doaj.art-02409129adc7494d8b094dca96e02b46 |
| institution | Directory Open Access Journal |
| issn | 2329-7778 |
| language | English |
| last_indexed | 2024-04-13T02:45:29Z |
| publishDate | 2018-11-01 |
| publisher | AIP Publishing LLC and ACA |
| record_format | Article |
| series | Structural Dynamics |
| spelling | doaj.art-02409129adc7494d8b094dca96e02b462022-12-22T03:06:03ZengAIP Publishing LLC and ACAStructural Dynamics2329-77782018-11-0156064101064101-2210.1063/1.5058172003806SDYThe impact of interior dielectric constant and entropic change on HIV-1 complex binding free energy predictionYuchen Li0Yalong Cong1Guoqiang Feng2Susu Zhong3John Z. H. Zhang4Huiyong Sun5Lili Duan6 School of Physics and Electronics, Shandong Normal University, Jinan 250014, China School of Physics and Electronics, Shandong Normal University, Jinan 250014, China School of Physics and Electronics, Shandong Normal University, Jinan 250014, China School of Physics and Electronics, Shandong Normal University, Jinan 250014, China Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China Department of Medicinal Chemistry, School of Pharmacy, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China School of Physics and Electronics, Shandong Normal University, Jinan 250014, ChinaAt present, the calculated binding free energy obtained using the molecular mechanics/Poisson-Boltzmann (Generalized-Born) surface area (MM/PB(GB)SA) method is overestimated due to the lack of knowledge of suitable interior dielectric constants in the simulation on the interaction of Human Immunodeficiency Virus (HIV-1) protease systems with inhibitors. Therefore, the impact of different values of the interior dielectric constant and the entropic contribution when using the MM/PB(GB)SA method to calculate the binding free energy was systemically evaluated. Our results show that the use of higher interior dielectric constants (1.4–2.0) can clearly improve the predictive accuracy of the MM/PBSA and MM/GBSA methods, and computational errors are significantly reduced by including the effects of electronic polarization and using a new highly efficient interaction entropy (IE) method to calculate the entropic contribution. The suitable range for the interior dielectric constant is 1.4–1.6 for the MM/PBSA method; within this range, the correlation coefficient fluctuates around 0.84, and the mean absolute error fluctuates around 2 kcal/mol. Similarly, an interior dielectric constant of 1.8–2.0 produces a correlation coefficient of approximately 0.76 when using the MM/GBSA method. In addition, the entropic contribution of each individual residue was further calculated using the IE method to predict hot-spot residues, and the detailed binding mechanisms underlying the interactions of the HIV-1 protease, its inhibitors, and bridging water molecules were investigated. In this study, the use of a higher interior dielectric constant and the IE method can improve the calculation accuracy of the HIV-1 system.http://dx.doi.org/10.1063/1.5058172 |
| spellingShingle | Yuchen Li Yalong Cong Guoqiang Feng Susu Zhong John Z. H. Zhang Huiyong Sun Lili Duan The impact of interior dielectric constant and entropic change on HIV-1 complex binding free energy prediction Structural Dynamics |
| title | The impact of interior dielectric constant and entropic change on HIV-1 complex binding free energy prediction |
| title_full | The impact of interior dielectric constant and entropic change on HIV-1 complex binding free energy prediction |
| title_fullStr | The impact of interior dielectric constant and entropic change on HIV-1 complex binding free energy prediction |
| title_full_unstemmed | The impact of interior dielectric constant and entropic change on HIV-1 complex binding free energy prediction |
| title_short | The impact of interior dielectric constant and entropic change on HIV-1 complex binding free energy prediction |
| title_sort | impact of interior dielectric constant and entropic change on hiv 1 complex binding free energy prediction |
| url | http://dx.doi.org/10.1063/1.5058172 |
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