An improved fragment-based quantum mechanical method for calculation of electrostatic solvation energy of proteins

Jia, Xiangyu; Wang, Xianwei; Liu, Jinfeng; Zhang, John Z. H.; Ye, Mei; He, Xiao

doi:10.1063/1.4833678

Cited by 37 publications

(40 citation statements)

References 86 publications

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“…The electrostatically embedded generalized molecular fractionation with conjugate caps (EE-GMFCC) method was employed to perform full QM calculations of electric field in KSI. The detailed description of the EE-GMFCC method can be found in our previous works [ 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ]. The calculations of the electrostatic potential by the EE-GMFCC method are the same as our previous work [ 16 ].…”

Section: Computational Approachesmentioning

confidence: 99%

An Ab Initio QM/MM Study of the Electrostatic Contribution to Catalysis in the Active Site of Ketosteroid Isomerase

Wang

2018

Molecules

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The electric field in the hydrogen-bond network of the active site of ketosteroid isomerase (KSI) has been experimentally measured using vibrational Stark effect (VSE) spectroscopy, and utilized to study the electrostatic contribution to catalysis. A large gap was found in the electric field between the computational simulation based on the Amber force field and the experimental measurement. In this work, quantum mechanical (QM) calculations of the electric field were performed using an ab initio QM/MM molecular dynamics (MD) simulation and electrostatically embedded generalized molecular fractionation with conjugate caps (EE-GMFCC) method. Our results demonstrate that the QM-derived electric field based on the snapshots from QM/MM MD simulation could give quantitative agreement with the experiment. The accurate calculation of the electric field inside the protein requires both the rigorous sampling of configurations, and a QM description of the electrostatic field. Based on the direct QM calculation of the electric field, we theoretically confirmed that there is a linear correlation relationship between the activation free energy and the electric field in the active site of wild-type KSI and its mutants (namely, D103N, Y16S, and D103L). Our study presents a computational protocol for the accurate simulation of the electric field in the active site of the protein, and provides a theoretical foundation that supports the link between electric fields and enzyme catalysis.

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Section: Computational Approachesmentioning

confidence: 99%

An Ab Initio QM/MM Study of the Electrostatic Contribution to Catalysis in the Active Site of Ketosteroid Isomerase

Wang

2018

Molecules

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“…The PCM is a popular continuum-solvent method for incorporation of solvent effect in quantum mechanical calculations of small molecules. However, although the PCM method was generalized to model the solvation effect of large proteins based on linear-scaling quantum mechanical methods 61 – 63 , it still has limitations, e.g., many discrete surface charges will be required in the PCM which makes the solution of linear equation difficult computationally and the effect of ion concentrations is not included in the PCM method. In this work, by combining with continuum-solvent model based on the Poisson-Boltzmann (PB) equation, the EE-GMFCC-CHG will be used to model the electrostatic solvation effects of large proteins.…”

Section: Methodsmentioning

confidence: 99%

“…The MD simulation was performed with Amber99SB force field 37 and TIP3P water model to handle the protein and solvent (the specific process of the MD simulation is the same as that in ref. 63 ). The conformations were selected from the trajectory every 100 ps.…”

Section: Methodsmentioning

confidence: 99%

A quantum mechanical computational method for modeling electrostatic and solvation effects of protein

Wang

Gao

et al. 2018

Sci Rep

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An efficient computational approach for modeling protein electrostatic is developed according to static point-charge model distributions based on the linear-scaling EE-GMFCC (electrostatically embedded generalized molecular fractionation with conjugate caps) quantum mechanical (QM) method. In this approach, the Electrostatic-Potential atomic charges are obtained from ab initio calculation of protein, both polarization and charge transfer effect are taken into consideration. This approach shows a significant improvement in the description of electrostatic potential and solvation energy of proteins comparing with current popular molecular mechanics (MM) force fields. Therefore, it has gorgeous prospect in many applications, including accurate calculations of electric field or vibrational Stark spectroscopy in proteins and predicting protein-ligand binding affinity. It can also be applied in QM/MM calculations or electronic embedding method of ONIOM to provide a better electrostatic environment.

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“…Antony and Grimme [ 28 ] also showed how DFT-D3 can be applied to complexes of up to a few thousand atoms via molecular fragmentation with conjugated caps (MFCC). For MFCC (further discussed in references [ 29 , 30 , 31 ]), the protein is decomposed into fragments, which are then capped with typical end groups. MFCC is found to work well for the artificial case of a neutral peptide, but convergence problems are found for fragments with multiple charges.…”

Section: Dispersion-corrected Density Functional Theory (Dft-d) Anmentioning

confidence: 99%

Recent Progress in Treating Protein–Ligand Interactions with Quantum-Mechanical Methods

Yilmazer

Korth

2016

IJMS

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We review the first successes and failures of a “new wave” of quantum chemistry-based approaches to the treatment of protein/ligand interactions. These approaches share the use of “enhanced”, dispersion (D), and/or hydrogen-bond (H) corrected density functional theory (DFT) or semi-empirical quantum mechanical (SQM) methods, in combination with ensemble weighting techniques of some form to capture entropic effects. Benchmark and model system calculations in comparison to high-level theoretical as well as experimental references have shown that both DFT-D (dispersion-corrected density functional theory) and SQM-DH (dispersion and hydrogen bond-corrected semi-empirical quantum mechanical) perform much more accurately than older DFT and SQM approaches and also standard docking methods. In addition, DFT-D might soon become and SQM-DH already is fast enough to compute a large number of binding modes of comparably large protein/ligand complexes, thus allowing for a more accurate assessment of entropic effects.

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An improved fragment-based quantum mechanical method for calculation of electrostatic solvation energy of proteins

Cited by 37 publications

References 86 publications

An Ab Initio QM/MM Study of the Electrostatic Contribution to Catalysis in the Active Site of Ketosteroid Isomerase

An Ab Initio QM/MM Study of the Electrostatic Contribution to Catalysis in the Active Site of Ketosteroid Isomerase

A quantum mechanical computational method for modeling electrostatic and solvation effects of protein

Recent Progress in Treating Protein–Ligand Interactions with Quantum-Mechanical Methods

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