Aqueous solvation from hydrocarbons to biomolecules: Microscopic approaches from reference interaction site model integral equation theory

Solvent-solvent and solute-solvent reference interaction site model (RISM) integral equations with the hypernetted chain (HNC)-like closures are fully solved for aqueous solvation of methane, ethane, propane, n-butane, alanine dipeptide and KcsA potassium channel, respectively, in the TIP3P explicit water model.; The most recent all-atom CHARMM96 force fields for alkanes are employed with a minor modification to the Lennard-Jones distance parameter σ and the atomic partial charges Z to fit the experimentally observed alkane hydration free energies at 25°C using the HNC-RISM methods. With such all-atom models, the hydration thermodynamic properties of these four alkanes in the temperature range (10–55°C) are well predicted and rather good agreement with experiments is obtained in the temperature range for the hydration free energies of all four alkanes; the molecular conformational equilibria of n-butane in water is better described than those with united-atom models; the microscopic alkane hydration structures are analyzed at more detailed level in terms of the atomic solute-solvent radial distribution functions (RDFs) and running coordination numbers. The effects of the alkane solutes on water structure in terms of the isothermal solute density derivatives of the water-water RDFs are analyzed as well.; The most recent all-atom CHARMM22 force fields for proteins is employed for alanine dipeptide and the solvation structures for its seven stable conformations, C_7eq, C_7ax , C₅, α_R, β, α _L and P_II in TIP3P water, respectively are analyzed in terms of the atomic solute-solvent RDFs. The solvation thermodynamics and the conformational dependence of alanine dipeptide in aqueous solutions are analyzed.; For the first time, the RISM integral equation theory is applied to analyze K+/Na+ selectivity of KcsA potassium channel. The selectivity of K+ over Na+ is analyzed from the point of view of solvation structure and solvation energetics.; The present thesis work shows that RISM integral equation theory is an efficient tool to characterize hydrophobic hydration and aqueous solvation of biomolecules. The all-atom models for solute molecules show their advantages in characterizing solvation structure at a more detailed level, better describing the molecular conformational equilibria in solutions and allowing more flexibility for optimizing the available nonbonded parameters to improve the predictions of the RISM theory for hydrophobic hydration thermodynamics.