Abstract
We present a set of Lennard-Jones parameters for classical, all-atom models of acetate and various alkylated and non-alkylated forms of sulfate, sulfonate and phosphate ions, optimized to reproduce their interactions with water and with the physiologically relevant sodium, ammonium and methylammonium cations. The parameters are internally consistent and are fully compatible with the Generalized Amber Force Field (GAFF), the AMBER force field for proteins, the accompanying TIP3P water model and the sodium model of Joung and Cheatham. The parameters were developed primarily relying on experimental information - hydration free energies and solution activity derivatives at 0.5 m concentration - with ab initio, gas phase calculations being used for the cases where experimental information is missing. The ab initio parameterization scheme presented here is distinct from other approaches because it explicitly connects gas phase binding energies to intermolecular interactions in solution. We demonstrate that the original GAFF/AMBER parameters often overestimate anion-cation interactions, leading to an excessive number of contact ion pairs in solutions of carboxylate ions, and to aggregation in solutions of divalent ions. GAFF/AMBER parameters lead to excessive numbers of salt bridges in proteins and of contact ion pairs between sodium and acidic protein groups, issues that are resolved by using the optimized parameters presented here.
Highlights
Monoatomic and small polyatomic ions are key players in many biological processes, such as DNA folding,1 blood coagulation and anti-coagulation,2,3 protein stability4 and protein crystallization.5 The molecular mechanisms by which ions act are currently incompletely understood, in part because inferring molecular scale details from the signals detected in experiment cannot be unambiguously done
The optimized parameters are presented in the Electronic supplementary information (ESI),† in.top/.itp format for gromacs users; the original values are shown as comments, to facilitate comparisons
For HSO4À, scanning of the eOH–OH or sOH–OH parameters would in principle be necessary but in practice was not done because the original GAFF13,30–32 parameters proved adequate
Summary
Monoatomic and small polyatomic ions are key players in many biological processes, such as DNA folding, blood coagulation and anti-coagulation, protein stability and protein crystallization. The molecular mechanisms by which ions act are currently incompletely understood, in part because inferring molecular scale details from the signals detected in experiment cannot be unambiguously done. Classical, fixed-charge force fields for biomolecules in water have been under evolution for decades and are quite successful at predicting binding affinities and the folded structure of small proteins, the self-assembly of phospholipid bilayers, the importance of electrostatics in DNA, and DNA–protein interactions.. Classical, fixed-charge force fields for biomolecules in water have been under evolution for decades and are quite successful at predicting binding affinities and the folded structure of small proteins, the self-assembly of phospholipid bilayers, the importance of electrostatics in DNA, and DNA–protein interactions.11,12 These force fields were parameterized against experimental observables that reflect the balance between ion– water, biomolecule–water and water–water interactions (e.g., free energies of hydration).. They are able to reproduce experimental osmotic pressures or solution activities at salt concentrations below 1 M,15–19 and in a few cases up to much higher concentrations. Simulations based
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