Including Electronic Screening in Classical Force Field of Zinc Ion for Biomolecular Simulations

Frate, Gianluca Del; Nikitin, Alexei

doi:10.1002/slct.201802864

Cited by 9 publications

(12 citation statements)

References 28 publications

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“…An accurate parameterization of metals in biological systems in the context of classical molecular dynamics simulations based on state-of-the-art nonpolarizable FF for biological systems (like, e.g., AMBER, CHARMM, OPLS, etc.) is a challenging task and a currently active research topic. − Modeling strategies for metals in protein simulations (including the nonbonded, bonded, cationic dummy atom, and combined models) have been recently reviewed in ref . Some examples of the application of these models to the zinc(II) ion have been listed in ref .…”

Section: Introductionmentioning

confidence: 99%

“…Several protocols have been proposed to derive the parameters for metal ions based on the nonbonded model. ,,,− Here, we describe a novel exportable procedure that we have applied to zinc(II)-loaded proteins where the metal is coordinated by four protein residues and no exogenous ligands (for brevity, we will refer to these sites as “tetra-coordinate”). The residues taken into account in this work are cysteine and/or histidine, which are common zinc(II) ligands, − representing about 70% of all physiologically relevant zinc(II) sites in the Protein Data Bank (PDB) .…”

Section: Introductionmentioning

confidence: 99%

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Upgrading and Validation of the AMBER Force Field for Histidine and Cysteine Zinc(II)-Binding Residues in Sites with Four Protein Ligands

Macchiagodena

Pagliai

Andreini

et al. 2019

J. Chem. Inf. Model.

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We developed and validated a novel force field in the context of the AMBER parameterization for the simulation of zinc(II)-binding proteins. The proposed force field assumes nonbonded spherical interactions between the central zinc(II) and the coordinating residues. A crucial innovative aspect of our approach is to account for the polarization effects of the cation by redefining the atomic charges of the coordinating residues and an adjustment of Lennard-Jones parameters of Zn-interacting atoms to reproduce mean distance distributions. The optimal transferable parametrization was obtained by performing accurate quantum mechanical calculations on a training set of high-quality protein structures, encompassing the most common folds of zinc(II) sites. The addressed sites contain a zinc(II) ion tetra-coordinated by histidine and cysteine residues and represent about 70% of all physiologically relevant zinc(II) sites in the Protein Data Bank. Molecular dynamics simulations with explicit solvent, carried out on several zinc(II)-binding proteins not included in the training set, show that our model for zinc(II) sites preserves the tetra-coordination of the metal site with remarkable stability, yielding zinc(II)−X mean distances similar to experimental data. Finally, the model was tested by evaluating the zinc(II)-binding affinities, using the alchemical free energy perturbation approach. The calculated dissociation constants correlate satisfactorily with the experimental counterpart demonstrating the validity and transferability of the proposed parameterization for zinc(II)-binding proteins.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Upgrading and Validation of the AMBER Force Field for Histidine and Cysteine Zinc(II)-Binding Residues in Sites with Four Protein Ligands

Macchiagodena

Pagliai

Andreini

et al. 2019

J. Chem. Inf. Model.

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“…As can be seen, the results from the NN/MM-RESP simulation are in better agreement with the experimental observation. For example, the position of the first peak of RDF from the MD simulation with the Amber ff03 force field is located at 1.93 Å, which is obviously smaller than the experimental value, while the position of the second peak of RDF from the MD simulation with the CHARMM 22 force field is obviously larger than the experimental value . Even for two more advanced force fields, Amoeba and QPCT, which effectively consider the polarization and charge transfer effect, their results still have some room for improvement.…”

Section: Resultsmentioning

confidence: 93%

Molecular Dynamics Simulation of Zinc Ion in Water with an ab Initio Based Neural Network Potential

Zhu

Zhang³

2019

J. Phys. Chem. A

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An artificial neural network provides the possibility to develop molecular potentials with both the efficiency of the classical molecular mechanics and the accuracy of the quantum chemical methods. Here, we develop an ab initio based neural network potential (NN/MM-RESP) to perform molecular dynamics study of zinc ion in liquid water. In this approach, the interaction energy, atomic forces, and atomic charges of zinc ion and water molecules in the first solvent shell are described by a neural network potential trained with energies and forces generated from density functional calculations. The predicted energies and forces from the NN potential show excellent agreement with the quantum chemistry calculations. Using this approach, we carried out molecular dynamics simulation to study the hydration of zinc ion in water. The experimentally observed zinc−water radial distribution function, as well as the X-ray absorption near edge structure spectrum, is well-reproduced by the MD simulation. Comparison of the results with other theoretical calculations is provided, and important features of the present approach are discussed. The neural network approach used in this study can be applied to construct potentials to study solvation of other metal ions, and its salient features can shed light on the development of more accurate molecular potentials for metal ions in other environments such as proteins.

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“…A recent ECC model specifically tailored for the zinc ion, developed by the authors and already cited in the Introduction, has been used in MD simulations in TIP3P water model and protein bioactive sites, with satisfactory performances in the analyzed cases . In this section, the performances of the new models here optimized for TIP3P water are investigated in SPC/E and TIP4P EW water models.…”

Section: Resultsmentioning

confidence: 99%

“…This approach has been fruitfully applied to the description of salts in water solution, to charged organic molecules and to the investigation of biological processes involving metal ions . In a work recently published by the present authors, the same theoretical procedure has been applied to model the zinc ion in water and within the active site of two zinc proteins. Performances have been compared with state‐of‐the‐art nonbonded models, showing a good reproduction of many experimental properties.…”

Section: Introductionmentioning

confidence: 99%

Development of Nonbonded Models for Metal Cations Using the Electronic Continuum Correction

Nikitin

Frate

2019

J Comput Chem

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The parametrization of classical nonbonded models of metal ions has been widely addressed in the recent years. Despite the continuous development of novel and more physically inspired functional forms, the 12‐6 Lennard‐Jones plus Coulomb potential is still the most adopted force field in molecular dynamics (MD) codes, owing to its simple form and easy implementation. However, due to the integer formal charge, unpolarizable force fields of ions may suffer from overestimated interatomic electrostatic interactions, leading to nonphysical clustering or repulsion between such full charges. The electronic continuum correction (ECC) can fix this problem through a simple inclusion of solvent polarization effects via ionic charge rescaling. In this work, the development of novel nonbonded models for mono, divalent, and highly charged metal ions is presented. For each metal species, the ionic charge has been scaled, according to the ECC. Lennard‐Jones parameters have been optimized using experimental structural and thermodynamic properties as target quantities. Performances of the proposed models are discussed and compared with the literature data, while transferability attitudes among different and well‐known water models are evaluated. © 2019 Wiley Periodicals, Inc.

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Including Electronic Screening in Classical Force Field of Zinc Ion for Biomolecular Simulations

Cited by 9 publications

References 28 publications

Upgrading and Validation of the AMBER Force Field for Histidine and Cysteine Zinc(II)-Binding Residues in Sites with Four Protein Ligands

Upgrading and Validation of the AMBER Force Field for Histidine and Cysteine Zinc(II)-Binding Residues in Sites with Four Protein Ligands

Molecular Dynamics Simulation of Zinc Ion in Water with an ab Initio Based Neural Network Potential

Development of Nonbonded Models for Metal Cations Using the Electronic Continuum Correction

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