Comparison of the water perturbations induced by two small organic solutes: ab initio calculations and molecular dynamics simulation

Abstract

Quantum mechanical ab initio calculations have been performed to evaluate the optimized geometry of trimethy1amine-N-oxide (TMAO) and t-butyl alcohol (TBA) and their interaction potentials with water. The latter have been used in extensive molecular dynamics simulations. Statistical analyses of t h e systems configurations suggest that the water molecules involved in hydration are more tightly coordinated by TMAO than by TBA. This affects t h e diffusion properties of the solutes and of the surrounding water molecules.

Molecular dynamics simulation of aqueous solutions of trimethylamine-N-oxide and tert-butyl alcohol

“…For the latter, a change was done in order to get a better agreement between the TMAO oxygen-water oxygen radial distribution functions (RDFs), g OO (r), averaged over a 3 Â 10 7 -move Metropolis Monte Carlo simulation based on previously calculated ab initio atom-atom pair potentials 24 and 500-ps NVT MM MD simulations of a system consisting of one TMAO and 504 water molecules. Comparison of the RDFs indicates that the parameters of the TIP3P water oxygen atom (i.e., the oxygen type OW) yield the best agreement for the positions of the g OO (r) first-peak maximum.…”

“…This figure shows that the water distribution around the solute hydrophobic moiety is markedly less evident for TBA than for TMAO, in agreement with previous results. 24 Moreover, the SDF for the latter is larger between adjacent methyl groups, indicating that the presence of the nitrogen atom partially neutralizes the hydrophobic effects of these groups, thus disfavoring the self-aggregation at higher solute concentrations. This characteristic is even more evident in the GB SDF suggesting that it could be a common feature of the quaternary ammonium osmolytes.…”

Binary Phases of Aliphatic N-Oxides and Water: Force Field Development and Molecular Dynamics Simulation

“…Based on results of earlier ab initio investigations, 27 atomic site charges were determined by fitting to the electrostatic potential (ESP charges) rather than from population analysis. The latter (see also ref 20) yields quite unphysical values particularly for the central N atom that carries a positive formal charge. We used gas phase results instead of, for instance, quantum-chemical reaction field techniques to allow for electronic polarization due to the environment in order to maintain compatibility with the parametrization strategy commonly used for solute species.…”

“…[12][13][14][15][16][17][18][19] To investigate into the molecular mechanism of these effects by computational methods such as molecular dynamics (MD) simulation techniques, a force field for mixed solvents composed of water and N-oxide species is required that is also compatible with available biopolymer potential energy functions. Noto et al 20 were the first who constructed a force field for a rigid TMAO model in the presence of an aqueous environment based on quantum-chemical calculations of TMAO and a single water molecule within the Hartree-Fock (HF) approximation. The TMAO-water interaction potential comprises a modified Coulomb term and a r -10 /r -4 /r -2 expression covering dispersion and repulsion where r means the site-site distance and has not been tested with respect to its performance for reproducing condensed phase experimental data.…”

“…The force field was then used in MD simulations of a single TMAO molecule in water. 20 Zou et al applied the force field with some adjustments in simulations at finite TMAO concentrations. 19 They found some evidence regarding changes of water-water structure and dynamics due to the N-oxide presence and related this result to the protein stabilization effect.…”