New Interaction Parameters for Charged Amino Acid Side Chains in the GROMOS Force Field

Abstract

A GROMOS force-field parameter set 54A8 is developed, which is based on the latest 54A7 set [Schmid et al. Eur. Biophys. J. 2011, 40, 843−856] and involves a recalibration of the nonbonded interaction parameters for the charged amino acid side chains, based on ionic side chain analogs. After a thorough analysis of the available experimental data, conventional hydration free energies for the ammonium; mono-, di-, tri-, and tetramethyl-ammonium; formate; acetate; propanoate; imidazolium; and guanidinium ions are combined with a standard absolute intrinsic proton hydration free energy ΔG hyd ⊖ [H g + ] = −1100 kJ•mol −1 to yield absolute intrinsic single-ion hydration free energies serving as experimental target data. The raw hydration free energies calculated from atomistic simulations are affected by electrostatic and finite-size artifacts, and corrections are applied to reach methodological independence prior to comparison with these experimental values. Except for monomethyl-ammonium, ions with parameters derived directly from the 54A7 force field considerably underestimate (ammonium, formate, acetate, propanoate, guanidinium) or overestimate (di-, tri-, and tetramethyl-ammonium; imidazolium) the magnitude of the intrinsic hydration free energy, the largest deviation affecting the acetate ion (40.0 kJ•mol −1 ). After reparameterization into 54A8, the mean and maximal absolute deviations between simulated and experimental data over the set of 10 ions are reduced from 23.1 and 40.0 kJ•mol −1 , respectively, to 1.8 and 6.3 kJ•mol −1 , respectively. Although the 54A7 and 54A8 parameter sets differ significantly in terms of the hydration free energies of the ions considered, other properties such as ion−water radial distribution functions and ion−ion potentials of mean force appear to be only moderately sensitive to this change. These properties are similar for the two sets and, in the case of the ion−water radial distribution functions, in good agreement with available experimental data.

All-Atom Continuous Constant pH Molecular Dynamics With Particle Mesh Ewald and Titratable Water

“…In contrast, the GRF-based data gives a sizable intercept of 0.77, indicative of a systematic overestimation of p K a shifts, which may be attributed, in part to the overstabilization of neutral states by GRF as shown in our previous work, 30 and in part to the lack of a finite-size correction as shown by Reif et al in simulations based on the Baker-Watts reaction field. 31,32 The hybrid-solvent data shows a slope well below one (0.61), indicative of a systematic underestimation of p K a shifts, which is due to the underestimation of desolvation penalty by the GBSW model (”too wet”). 8,9,57 The above-mentioned trend can also be seen from the histogram of p K a deviations, p K a calc - p K a expt (Fig.…”

“…29 Second, our previous analysis showed force shifting or GRF-based CpHMD favors neutral species in titration due to the underestimation of favorable charging free energies and solvation free energies of charged solutes. 30 This may be a major cause for the systematic overestimation of p K a shifts of buried residues, 25 although we acknowledge that the deviations may be reduced by performing the finite-size correction for charging free energies as shown by Reif et al 31,32 in the context of simulations with the Baker-Watts reaction field. 28 Lastly, although it remains somewhat debatable as to whether PME outperforms GRF for charged proteins, 33,34 PME is arguably the most widely used electrostatic method in MD simulations, and the highly parallel as well as GPU versions have been implemented in all major molecular dynamics packages such as AMBER, 35 CHARMM 20 and GROMACS.…”

Ion Association in Hydrothermal Sodium Sulfate Solutions Studied by Modulated FT-IR-Raman Spectroscopy and Molecular Dynamics

“…44 Models for the sodium and sulfate ions are included in this forcefield version as well as the SPC/E 45 model for the water. This water model was chosen because of it Jones parameters for the atoms are given in Table 1: The density of the simulation box was set to the experimental values from Khaibullin et al 48 After an energy minimization of the simulation box at 0 K, the temperature was increased to the desired value and the system was equilibrated for 2 ns.…”

A GROMOS-Compatible Force Field for Small Organic Molecules in the Condensed Phase: The 2016H66 Parameter Set

“…Condensed-phase force fields such as CHARMM [5][6][7][8][9][10][11][12][13][14][15] , AMBER [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] , OPLS 32-44 , TraPPE [45][46][47][48][49][50][51][52] and GROMOS [53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68] mainly aim at the description of solids, liquids and solutions, including solvated biomolecules as a particularly relevant special case. ...…”