This review surveys mainly recent computer simulations for exploring the
structure of solutions with small organic solutes in water and organic solvents. The solute’s
geometry may be optimized at a high quantum mechanical level if some polarizable
continuum-solvent method is utilized and then kept constant throughout subsequent
simulations. In-solution geometry optimization is especially important in cases where only
the environment stabilizes the structure, e.g., the zwitterionic form for amino acids in water.
For solutes subject to conformational/tautomeric equilibria separate modeling is needed if
rigid geometries are considered. In contrast, finding adequate intramolecular force-field
parameters for torsional potentials, non-bonded van der Waals interactions and consideration of the
electrostatic-potential-derived net atomic charges through the calculation of the Coulombic interactions are
key issues in molecular dynamics simulations with flexible solute geometries. Furthermore, relative
conformational energies can change greatly depending on the solvent and/or protein/membrane environment,
thus the applied force-field has to account for their effects. Proper choice for the protonation state of acidic or
basic solutes and assuring the required concentration are important simulation conditions, as well, for
obtaining relevant models. The solution structures could be ultimately characterized by calculating different
distribution functions and applying specifically developed statistics. Potential of mean force curves usefully
follow the free energy changes through solute dimerization. Results of experimental studies using different
spectroscopic and diffraction methods have been compared with those from theoretical simulations.
Keywords: Conformers, force fields, hydrogen bonds, molecular dynamics, Monte Carlo, solute and
solvent modeling, structure statistics, tautomers.
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