Automated Fragmentation QM/MM Calculation of NMR Chemical Shifts for Protein-Ligand Complexes
In this study, the automated fragmentation quantum mechanics/molecular mechanics (AF-QM/MM) method was applied for NMR chemical shift calculations of protein-ligand complexes. In the AF-QM/MM approach, the protein binding pocket is automatically divided into capped fragments (within ~200 atoms) for...
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Frontiers Media S.A.
2018-05-01
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| Series: | Frontiers in Chemistry |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fchem.2018.00150/full |
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| author | Xinsheng Jin Tong Zhu Tong Zhu John Z. H. Zhang John Z. H. Zhang John Z. H. Zhang Xiao He Xiao He Xiao He |
| author_facet | Xinsheng Jin Tong Zhu Tong Zhu John Z. H. Zhang John Z. H. Zhang John Z. H. Zhang Xiao He Xiao He Xiao He |
| author_sort | Xinsheng Jin |
| collection | DOAJ |
| description | In this study, the automated fragmentation quantum mechanics/molecular mechanics (AF-QM/MM) method was applied for NMR chemical shift calculations of protein-ligand complexes. In the AF-QM/MM approach, the protein binding pocket is automatically divided into capped fragments (within ~200 atoms) for density functional theory (DFT) calculations of NMR chemical shifts. Meanwhile, the solvent effect was also included using the Poission-Boltzmann (PB) model, which properly accounts for the electrostatic polarization effect from the solvent for protein-ligand complexes. The NMR chemical shifts of neocarzinostatin (NCS)-chromophore binding complex calculated by AF-QM/MM accurately reproduce the large-sized system results. The 1H chemical shift perturbations (CSP) between apo-NCS and holo-NCS predicted by AF-QM/MM are also in excellent agreement with experimental results. Furthermore, the DFT calculated chemical shifts of the chromophore and residues in the NCS binding pocket can be utilized as molecular probes to identify the correct ligand binding conformation. By combining the CSP of the atoms in the binding pocket with the Glide scoring function, the new scoring function can accurately distinguish the native ligand pose from decoy structures. Therefore, the AF-QM/MM approach provides an accurate and efficient platform for protein-ligand binding structure prediction based on NMR derived information. |
| first_indexed | 2024-04-11T23:10:54Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2296-2646 |
| language | English |
| last_indexed | 2024-04-11T23:10:54Z |
| publishDate | 2018-05-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Chemistry |
| spelling | doaj.art-6dc6ff8b00de402896bfb1d620381fe52022-12-22T03:57:51ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462018-05-01610.3389/fchem.2018.00150357486Automated Fragmentation QM/MM Calculation of NMR Chemical Shifts for Protein-Ligand ComplexesXinsheng Jin0Tong Zhu1Tong Zhu2John Z. H. Zhang3John Z. H. Zhang4John Z. H. Zhang5Xiao He6Xiao He7Xiao He8State Key Laboratory of Precision Spectroscopy, School of Chemistry and Molecular Engineering, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, East China Normal University, Shanghai, ChinaState Key Laboratory of Precision Spectroscopy, School of Chemistry and Molecular Engineering, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, East China Normal University, Shanghai, ChinaNYU-ECNU Center for Computational Chemistry at NYU Shanghai, Shanghai, ChinaState Key Laboratory of Precision Spectroscopy, School of Chemistry and Molecular Engineering, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, East China Normal University, Shanghai, ChinaNYU-ECNU Center for Computational Chemistry at NYU Shanghai, Shanghai, ChinaDepartment of Chemistry, New York University, New York, NY, United StatesState Key Laboratory of Precision Spectroscopy, School of Chemistry and Molecular Engineering, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, East China Normal University, Shanghai, ChinaNYU-ECNU Center for Computational Chemistry at NYU Shanghai, Shanghai, ChinaNational Engineering Research Centre for Nanotechnology, Shanghai, ChinaIn this study, the automated fragmentation quantum mechanics/molecular mechanics (AF-QM/MM) method was applied for NMR chemical shift calculations of protein-ligand complexes. In the AF-QM/MM approach, the protein binding pocket is automatically divided into capped fragments (within ~200 atoms) for density functional theory (DFT) calculations of NMR chemical shifts. Meanwhile, the solvent effect was also included using the Poission-Boltzmann (PB) model, which properly accounts for the electrostatic polarization effect from the solvent for protein-ligand complexes. The NMR chemical shifts of neocarzinostatin (NCS)-chromophore binding complex calculated by AF-QM/MM accurately reproduce the large-sized system results. The 1H chemical shift perturbations (CSP) between apo-NCS and holo-NCS predicted by AF-QM/MM are also in excellent agreement with experimental results. Furthermore, the DFT calculated chemical shifts of the chromophore and residues in the NCS binding pocket can be utilized as molecular probes to identify the correct ligand binding conformation. By combining the CSP of the atoms in the binding pocket with the Glide scoring function, the new scoring function can accurately distinguish the native ligand pose from decoy structures. Therefore, the AF-QM/MM approach provides an accurate and efficient platform for protein-ligand binding structure prediction based on NMR derived information.http://journal.frontiersin.org/article/10.3389/fchem.2018.00150/fullAF-QMMMNMR chemical shiftprotein-ligand bindingscoring functionstructure prediction |
| spellingShingle | Xinsheng Jin Tong Zhu Tong Zhu John Z. H. Zhang John Z. H. Zhang John Z. H. Zhang Xiao He Xiao He Xiao He Automated Fragmentation QM/MM Calculation of NMR Chemical Shifts for Protein-Ligand Complexes Frontiers in Chemistry AF-QMMM NMR chemical shift protein-ligand binding scoring function structure prediction |
| title | Automated Fragmentation QM/MM Calculation of NMR Chemical Shifts for Protein-Ligand Complexes |
| title_full | Automated Fragmentation QM/MM Calculation of NMR Chemical Shifts for Protein-Ligand Complexes |
| title_fullStr | Automated Fragmentation QM/MM Calculation of NMR Chemical Shifts for Protein-Ligand Complexes |
| title_full_unstemmed | Automated Fragmentation QM/MM Calculation of NMR Chemical Shifts for Protein-Ligand Complexes |
| title_short | Automated Fragmentation QM/MM Calculation of NMR Chemical Shifts for Protein-Ligand Complexes |
| title_sort | automated fragmentation qm mm calculation of nmr chemical shifts for protein ligand complexes |
| topic | AF-QMMM NMR chemical shift protein-ligand binding scoring function structure prediction |
| url | http://journal.frontiersin.org/article/10.3389/fchem.2018.00150/full |
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