Systematic Parameterization of Monovalent Ions Employing the Nonbonded Model

Li, Pengfei; Song, Lin Frank; Merz, Kenneth M.

doi:10.1021/ct500918t

Cited by 370 publications

(517 citation statements)

References 112 publications

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“…The amber ff14SB force fields38 were used to describe the atomic interactions involving the protein and nucleic acids, and the recently developed ion parameter sets optimized in TIP3P water3940 were selected for the mono- and divalent ions. It is noted that none of the available non-bonded models for Mg 2+ ion is able to reproduce various experimental properties simultaneously; the set of Mg 2+ parameters here represent the best possible compromise targeting the experimental Mg-O distance, hydration free energy as well as coordination number40.…”

Section: Methodsmentioning

confidence: 99%

Cas9-catalyzed DNA Cleavage Generates Staggered Ends: Evidence from Molecular Dynamics Simulations

Zuo

Liu

2016

Sci Rep

120

133

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The CRISPR-associated endonuclease Cas9 from Streptococcus pyogenes (spCas9) along with a single guide RNA (sgRNA) has emerged as a versatile toolbox for genome editing. Despite recent advances in the mechanism studies on spCas9-sgRNA-mediated double-stranded DNA (dsDNA) recognition and cleavage, it is still unclear how the catalytic Mg2+ ions induce the conformation changes toward the catalytic active state. It also remains controversial whether Cas9 generates blunt-ended or staggered-ended breaks with overhangs in the DNA. To investigate these issues, here we performed the first all-atom molecular dynamics simulations of the spCas9-sgRNA-dsDNA system with and without Mg2+ bound. The simulation results showed that binding of two Mg2+ ions at the RuvC domain active site could lead to structurally and energetically favorable coordination ready for the non-target DNA strand cleavage. Importantly, we demonstrated with our simulations that Cas9-catalyzed DNA cleavage produces 1-bp staggered ends rather than generally assumed blunt ends.

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Section: Methodsmentioning

confidence: 99%

Cas9-catalyzed DNA Cleavage Generates Staggered Ends: Evidence from Molecular Dynamics Simulations

Zuo

Liu

2016

Sci Rep

120

133

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“…Just like ionic radii, these are elusive quantities, as can be judged by the numerous parametrizations available. 1,57,59,63,[65][66][67][68][69][70][71][72][73][74][75][76][77][78][79][80] The latter issue could in principle be addressed by moving to quantum-mechanical (QM) models, where the ionsolvent interactions are determined on the basis of fundamental physics instead of empirical parameters. In addition, the QM description is expected to further improve the representation of short-range ion-solvent interactions (more accurate description of specific ion-solvent interactions, from pairwiseadditive in MM to now include electronic polarization, charge transfer, and other many-body effects).…”

Section: Introductionmentioning

confidence: 99%

Absolute proton hydration free energy, surface potential of water, and redox potential of the hydrogen electrode from first principles: QM/MM MD free-energy simulations of sodium and potassium hydration

Hofer

Hünenberger

2018

The Journal of Chemical Physics

104

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The absolute intrinsic hydration free energy G • H + ,wat of the proton, the surface electric potential jump χ • wat upon entering bulk water, and the absolute redox potential V • H + ,wat of the reference hydrogen electrode are cornerstone quantities for formulating single-ion thermodynamics on absolute scales. They can be easily calculated from each other but remain fundamentally elusive, i.e., they cannot be determined experimentally without invoking some extra-thermodynamic assumption (ETA). The Born model provides a natural framework to formulate such an assumption (Born ETA), as it automatically factors out the contribution of crossing the water surface from the hydration free energy. However, this model describes the short-range solvation inaccurately and relies on the choice of arbitrary ion-size parameters. In the present study, both shortcomings are alleviated by performing first-principle calculations of the hydration free energies of the sodium (Na + ) and potassium (K + ) ions. The calculations rely on thermodynamic integration based on quantum-mechanical molecular-mechanical (QM/MM) molecular dynamics (MD) simulations involving the ion and 2000 water molecules. The ion and its first hydration shell are described using a correlated ab initio method, namely resolution-of-identity second-order Møller-Plesset perturbation (RIMP2). The next hydration shells are described using the extended simple point charge water model (SPC/E). The hydration free energy is first calculated at the MM level and subsequently increased by a quantization term accounting for the transformation to a QM/MM description. It is also corrected for finite-size, approximate-electrostatics, and potentialsummation errors, as well as standard-state definition. These computationally intensive simulations provide accurate first-principle estimates for G • H + ,wat , χ • wat , and V • H + ,wat , reported with statistical errors based on a confidence interval of 99%. The values obtained from the independent Na + and K + simulations are in excellent agreement. In particular, the difference between the two hydration free energies, which is not an elusive quantity, is 73.9 ± 5.4 kJ mol 1 (K + minus Na + ), to be compared with the experimental value of 71.7 ± 2.8 kJ mol 1 . The calculated values of G • H + ,wat , χ • wat , and V • H + ,wat ( 1096.7 ± 6.1 kJ mol 1 , 0.10 ± 0.10 V, and 4.32 ± 0.06 V, respectively, averaging over the two ions) are also in remarkable agreement with the values recommended by Reif and Hünenberger based on a thorough analysis of the experimental literature ( 1100 ± 5 kJ mol 1 , 0.13 ± 0.10 V, and 4.28 ± 0.13 V, respectively). The QM/MM MD simulations are also shown to provide an accurate description of the hydration structure, dynamics, and energetics. Published by AIP Publishing.

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“…As in the case of the TATB, the authors did not specify whether these values included the surface potential contribution. Even though the authors justify their assumption using arguments about gas phase cluster-ion properties (which include the surface potential contribution [20]), the resulting values have been treated as intrinsic quantities and used as a basis for the development of an alkali halide-water force field by Joung and Cheatham [51], and more recently by Li et al [91] The authors also attempted to derive single-ion hydration thermodynamics by assuming the linear relationship between hydration enthalpies and entropies discussed in Section 3.2 (Fig. 4), and arrived at values…”

Section: Equal Entropy Assumptionmentioning

confidence: 99%

“…Since the hydration free energies are closely related to the size of the ion, the resulting models also differ significantly in the structural properties. More recently Li et al combined reference values for alkali metal cations derived from TATB ETA and halide anions derived from the equalentropy ETA [91], a combination that makes the resulting models unable to reproduce the neutral salt properties.…”

Section: Bulk Solutionsmentioning

confidence: 99%

“…The largest group of the empirical models conforms to the same type of ion-water interactions, and consist of the Lennard-Jones (LJ) potential acting between the ion and water oxygen, complemented by point charge (PC) interactions between the ion and water oxygen and hydrogens [25,26,66,83,91,97,[153][154][155][156][157][158][159][160]. We will denote this force field form as LJPC.…”

Section: Bulk Solutionsmentioning

confidence: 99%

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Single-ion hydration thermodynamics from clusters to bulk solutions: Recent insights from molecular modeling

Vlček

Chialvo

2016

Fluid Phase Equilibria

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A B S T R A C TThe importance of single-ion hydration thermodynamic properties for understanding the driving forces of aqueous electrolyte processes, along with the impossibility of their direct experimental measurement, have prompted a large number of experimental, theoretical, and computational studies aimed at separating the cation and anion contributions. Here we provide an overview of historical approaches based on extrathermodynamic assumptions and more recent computational studies of single-ion hydration in order to evaluate the approximations involved in these methods, quantify their accuracy, reliability, and limitations in the light of the latest developments. We also offer new insights into the factors that influence the accuracy of ion-water interaction models and our views on possible ways to fill this substantial knowledge gap in aqueous physical chemistry.

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Systematic Parameterization of Monovalent Ions Employing the Nonbonded Model

Cited by 370 publications

References 112 publications

Cas9-catalyzed DNA Cleavage Generates Staggered Ends: Evidence from Molecular Dynamics Simulations

Cas9-catalyzed DNA Cleavage Generates Staggered Ends: Evidence from Molecular Dynamics Simulations

Absolute proton hydration free energy, surface potential of water, and redox potential of the hydrogen electrode from first principles: QM/MM MD free-energy simulations of sodium and potassium hydration

Single-ion hydration thermodynamics from clusters to bulk solutions: Recent insights from molecular modeling

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