A Combined Experimental and Theoretical Study of Ion Solvation in Liquid N-Methylacetamide

Abstract

Most current biomolecular simulations are based on potential energy functions that treat the electrostatic energy as a sum of pairwise Coulombic interactions between effective fixed atomic charges. This approximation, in which many-body induced polarization effects are included in an average way, is expected to be satisfactory for a wide range of systems, but less accurate for processes involving the transfer and partition of ions among heterogeneous environments. The limitations of these potential energy functions are perhaps most obvious in studies of ion permeation through membrane channels. In many cases, the pore is so narrow that the permeating ion must shed most of its surrounding water molecules and the large energetic loss due to dehydration must be compensated by coordination with protein atoms. Interactions of cations with protein backbone carbonyl oxygens, in particular, play a critical role in several important biological channels. As a first step toward meeting the challenge of developing an accurate explicit accounting for induced polarization effects, the present work combines experiments and computation to characterize the interactions of alkali and halide ions with N-methylacetamide chosen to represent the peptide bond. From solubility measurements, we extract the solvation free energies of KCl and NaCl in liquid N-methylacetamide. Polarizable models based on the Drude oscillator are then developed and compared with available experimental and ab initio data. The good agreement for a range of structural and thermodynamic properties in the gas and condensed phases suggests that the polarizable models provide an accurate representation of ion–amide interactions in biological systems.

How does overcoordination create ion selectivity?

“…This is realised through the interplay of the ion-ligand and ligand-ligand interactions as the number of coordinating ligands changes. This investigation differs from previous work [13,14,35] as it elucidates through what mechanism this interplay of interactions leads to selectivity by overcoordination, rather than simply stating that it does. This work also does not attempt to answer the questions of the role of overcoordination in particular molecules, or how molecules are able to enforce the necessary conditions for overcoordination to arise (questions 1 and 2 in the Introduction), as it is the question of how enforcing a coordination number gives rise to ion selectivity that we wish to elucidate and clarify.…”

Challenges and advances in atomistic simulations of potassium and sodium ion channel gating and permeation

“…Thus, development of vdW parameters for specific interactions involving ions has been performed (see, e.g. Berneche & Roux, 2001;Luo & Roux, 2009;Venable et al 2013;Kahlen et al 2014;Li et al 2015 experimental salt solubilities (Yu et al 2010), ion pair formation/dissociation constants (Kahlen et al 2014), salt solution osmotic pressures (Luo & Roux, 2009) and charged membrane electrophoretic mobilities (Venable et al 2013), typically combined with gas-phase and/or condensed-phase QM calculations are used instead.…”

“…Therefore, surrogate markers, such as experimental salt solubilities (Yu et al . ), ion pair formation/dissociation constants (Kahlen et al . ), salt solution osmotic pressures (Luo & Roux, ) and charged membrane electrophoretic mobilities (Venable et al .…”

Six-site polarizable model of water based on the classical Drude oscillator

“…Specifically, the models have a good balance between the treatment of single, clustered, and bulk phase water, and perform well in simulations under ambient conditions. [28][29][30] However, some drawbacks are also present that motivated the present effort. First, in the development of the SWM4 models, the diffusion coefficient, which was used as target data, was evaluated without system size correction.…”