From Microscopic Monte-Carlo Simulations to Macroscopic Solvation Models (original) (raw)
Related papers
1997
We describe atomistic simulations of the free energy and entropy of hydration of ions in aqueous solution at 25 °C using a simple point charge model (SPC/E) for water and charged spherical Lennard-Jones solutes. We use a novel method with an extended Lagrangian or Hamiltonian in which the charge and the size of the ions are considered as dynamical variables. This enables us to determine thermodynamic properties as continuous functions of solute size and charge and to move smoothly from hydrophilic to hydrophobic solvation conditions. On passing between these extremes, the entropy of solvation goes through maxima. For example it shows a double maximum as a function of charge at constant size and a single maximum as a function of size at constant (non-zero) charge. These maxima correspond to extremes of structure-breaking and are associated with the disappearance of the second solvation shell in the radial distribution function; no anomalies are seen in the first shell. We also presen...
Relative Free Energies for Hydration of Monovalent Ions from QM and QM:MM Simulations
Methods directly evaluating the hydration structure and thermodynamics of physiologically relevant cations (Na + , K + , Cl − , etc.) have wide ranging applications in the fields of inorganic, physical, and biological chemistry. All-atom simulations based on accurate potential energy surfaces appear to offer a viable option for assessing the chemistry of ion solvation. Although MD and free energy simulations of ion solvation with classical force fields have proven their usefulness, a number of challenges still remain. One of them is the difficulty of force field benchmarking and validation against structural and thermodynamic data obtained for a condensed phase. Hybrid quantum mechanical/molecular mechanical (QM/MM) models combined with sampling algorithms have the potential to provide an accurate solvation model and to incorporate the effects from the surrounding, which is often missing in gas-phase ab initio computations. Herein, we report the results from QM/MM free energy simulations of Na + /K + and Cl − /Br − hydration where we simultaneously characterized the relative thermodynamics of ion solvation and changes in the solvation structure. The Flexible Inner Region Ensemble Separator (FIRES) method was used to impose a spatial separation between QM region and the outer sphere of solvent molecules treated with the CHARMM27 force field. FEP calculations based on QM/MM simulations utilizing the CHARMM/deMon2k interface were performed with different basis set combinations for K + /Na + and Cl − /Br − perturbations to establish the dependence of the computed free energies on the basis set level. The dependence of the computed relative free energies on the size of the QM and MM regions is discussed. The current methodology offers an accurate description of structural and thermodynamic aspects of the hydration of alkali and halide ions in neat solvents and can be used to obtain thermodynamic data on ion solvation in condensed phase along with underlying structural properties of the ion−solvent system. Figure 11. Oxygen−ion−oxygen ADF for Cl − and Br − simulations with polarizable force field (Drude), QM, and QM/MM systems. Journal of Chemical Theory and Computation Article dx.doi.org/10.1021/ct400296w | J. Chem. Theory Comput. 2013, 9, 4165−4175
International Journal of Quantum Chemistry, 2004
Free energies of hydration (FEH) have been computed for 13 neutral and nine ionic species as a difference of theoretically calculated Gibbs free energies in solution and in the gas phase. In-solution calculations have been performed using both SCIPCM and PCM polarizable continuum models at the density functional theory (DFT)/B3LYP and ab initio Hartree-Fock levels with two basis sets (6-31G* and 6-311ϩϩG**). Good linear correlation has been obtained for calculated and experimental gas-phase dipole moments, with an increase by ϳ30% upon solvation due to solute polarization. The geometry distortion in solution turns out to be small, whereas solute polarization energies are up to 3 kcal/mol for neutral molecules. Calculation of free energies of hydration with PCM provides a balanced set of values with 6-31G* and 6-311ϩϩG** basis sets for neutral molecules and ionic species, respectively. Explicit solvent calculations within Monte Carlo simulations applying free energy perturbation methods have been considered for 12 neutral molecules. Four different partial atomic charge sets have been studied, obtained by a fit to the gas-phase and in-solution molecular electrostatic potentials at in-solution optimized geometries. Calculated FEH values depend on the charge set and the atom model used. Results indicate a preference for the all-atom model and partial charges obtained by a fit to the molecular electrostatic potential of the solute computed at the SCIPCM/B3LYP/6-31G* level.
Computation of hydration free energies of organic solutes with an implicit water model
Journal of Computational Chemistry, 2006
A new approach for computing hydration free energies ⌬G solv of organic solutes is formulated and parameterized. The method combines a conventional PCM (polarizable continuum model) computation for the electrostatic component ⌬G el of ⌬G solv and a specially detailed algorithm for treating the complementary nonelectrostatic contributions (⌬G nel ). The novel features include the following: (a) two different cavities are used for treating ⌬G el and ⌬G nel . For the latter case the cavity is larger and based on thermal atomic radii (i.e., slightly reduced van der Waals radii). (b) The cavitation component of ⌬G nel is taken to be proportional to the volume of the large cavity. (c) In the treatment of van der Waals interactions, all solute atoms are counted explicitly. The corresponding interaction energies are computed as integrals over the surface of the larger cavity; they are based on Lennard Jones (LJ) type potentials for individual solute atoms. The weighting coefficients of these LJ terms are considered as fitting parameters. Testing this method on a collection of 278 uncharged organic solutes gave satisfactory results. The average error (RMSD) between calculated and experimental free energy values varies between 0.15 and 0.5 kcal/mol for different classes of solutes. The larger deviations found for the case of oxygen compounds are probably due to a poor approximation of H-bonding in terms of LJ potentials. For the seven compounds with poorest fit to experiment, the error exceeds 1.5 kcal/mol; these outlier points were not included in the parameterization procedure. Several possible origins of these errors are discussed. Figure 3. (a) Calculated [⌬G nel (calc)] and experimental [⌬G nel (exp)] nonelectrostatic components of solvation free energies in kcal/mol for aromatic and nitrogen compounds. (b) Calculated [⌬G nel (calc)] and experimental [⌬G nel (exp)] nonelectrostatic components of solvation free energies in kcal/mol for aromatic and nitrogen compounds. ⌬G el calculated with DMol 3 . compounds: ethers and alcohols. (b) Calculated [⌬G nel (calc)] and experimental [⌬G nel (exp)] nonelectrostatic components of solvation free energies in kcal/mol for oxygen compounds: esters and carbonyl groups. (c) Calculated [⌬G nel (calc)] and experimental [⌬G nel (exp)] nonelectrostatic components of solvation free energies in kcal/mol for oxygen compounds: ethers and alcohols. ⌬G el calculated with DMol 3 .
MST Continuum Study of the Hydration Free Energies of Monovalent Ionic Species
The Journal of Physical Chemistry B, 2005
In this study, we revisit the protocol previously proposed within the framework of the Miertus-Scrocco-Tomasi (MST) continuum model to define the cavity between the solute and solvent for predicting hydration free energies of univalent ions Luque, F. J. Chem. Phys. 1994, 182, 237]. The protocol relies on the use of a reduced cavity (around 10-15% smaller than the cavity used for neutral compounds) around the atom(s) bearing the formal charge. The suitability of this approach is examined here for a series of 47 univalent ions for which accurate experimental hydration free energies are available. Attention is also paid to the effect of the charge renormalization protocol used to correct uncertainties arising from the electron density located outside the solute cavity. The method presented here provides, with a minimum number of fitted parameters, reasonable estimates within the experimental error of the hydration free energy of ions (average relative error of 4.7%) and is able to reproduce solvation in water of both small and large ions.
The Journal of Physical Chemistry
The solvation free energies evaluated from molecular simulations with explicit solvent models and integral equation methods are compared to the results obtained from macroscopic models. Different parameter coupling schemes commonly used in free-energy simulations are analyzed. For the electrostatic and van der Waals contribution to the free energies of solvation, the macroscopic models suggest coupling schemes that can significantly reduce the time required for free energy simulations. A comparison of Poisson-Boltzmann calculations for solvation free energies with the Born-Kirkwood-Onsager multipole expansion method indicates that the former is a significant improvement for quantitative calculations of polyatomic solutes. However, the multipole expansion is useful for obtaining qualitative insights concerning the dependence of the solvation free energy on the characteristics of the charge distribution. The integral equation results for hydrophobic solvation have a surface area dependence with a proportionality factor, the effective "surface tension", that depends on the nature of the solute. The behavior of the solvation free energy in the limit of a vanishing hydrophobic solute is shown to lead to a small deviation from the simple surface area dependence.
Predictions of Hydration Free Energies from All-Atom Molecular Dynamics Simulations †
The Journal of Physical Chemistry B, 2009
Here, we computed the aqueous solvation (hydration) free energies of 52 small drug-like molecules using an all-atom force field in explicit water. This differs from previous studies in that: (1) this was a blind test (in an event called SAMPL sponsored by OpenEye Software), and (2) the test compounds were considerably more challenging than have been used in the past in typical solvation tests of allatom models. Overall, we found good correlations with experimental values which were subsequently made available, but the variances are large compared to in previous tests. We tested several different charge models, and found that several standard charge models performed relatively well. We found that hypervalent sulfur and phosphorous compounds are not well handled using current force field parameters, and suggest several other possible systematic errors. Overall, blind tests like these appear to provide significant opportunities for improving force fields and solvent models.
The Journal of Physical Chemistry B, 2000
The absolute solvation free energy of the hydroxide ion in aqueous solution was calculated by Monte Carlo simulation and free energy perturbation. We have used the TIP3P model for water and the solute-solvent interaction was modeled as an effective two-body potential of charge-charge plus Lennard-Jones terms fitted to reproduce the interaction energy in the OH -(H 2 O) 3 and OH -(H 2 O) 4 ionic clusters. The electrostatic contribution to the solvation free energy was determined by using solvent boxes having 120, 160, 216, 350, and 512 water molecules, and the limit for N approaching infinity was obtained by an extrapolation procedure. The final solvation free energy obtained by considering the Lennard-Jones potential contribution, correcting for the cutoff surface potential, and including the surface potential of water cluster amounts to -108.0 kcal mol -1 , in very good agreement with the experimental value of -105.0 kcal mol -1 . This result shows that the extrapolation method coupled with the use of an effective two-body potential is a viable and accurate procedure for calculating the absolute solvation free energy of ionic species.
Using molecular dynamics free energy simulations with TIP3P explicit solvent, we compute the hydration free energies of 504 neutral small organic molecules and compare them to experiments. We find, first, good general agreement between the simulations and the experiments, with an rms error of 1.24 kcal/mol over the whole set (i.e., about 2 kT) and a correlation coefficient of 0.89. Second, we use an automated procedure to identify systematic errors for some classes of compounds and suggest some improvements to the force field. We find that alkyne hydration free energies are particularly poorly predicted due to problems with a Lennard-Jones well depth and find that an alternate choice for this well depth largely rectifies the situation. Third, we study the nonpolar component of hydration free energiessthat is, the part that is not due to electrostatics. While we find that repulsive and attractive components of the nonpolar part both scale roughly with surface area (or volume) of the solute, the total nonpolar free energy does not scale with the solute surface area or volume, because it is a small difference between large components and is dominated by the deviations from the trend. While the methods used here are not new, this is a more extensive test than previous explicit solvent studies, and the size of the test set allows identification of systematic problems with force field parameters for particular classes of compounds. We believe that the computed free energies and components will be valuable to others in the future development of force fields and solvation models.
Free energy of ion hydration: Interface susceptibility and scaling with the ion size
The Journal of Chemical Physics, 2015
Free energy of solvation of a spherical ion in a force-field water is studied by numerical simulations. The focus is on the linear solvation susceptibility connecting the linear response solvation free energy to the squared ion charge. Spherical hard-sphere solutes, hard-sphere ions, and Kihara solutes (Lennard-Jones modified hard-sphere core) are studied here. The scaling of the solvation susceptibility with the solute size significantly deviates from the Born equation. Using empirical offset corrections of the solute size (or the position of the first peak of the solute-solvent distribution function) do not improve the agreement with simulations. We advance a new perspective on the problem by deriving an exact relation for the radial susceptibility function of the interface. This function yields an effective cavity radius in the Born equation calculated from the solute-solvent radial distribution function. We find that the perspective of the local response, assuming significant al...