Solvation structure, thermodynamics, and conformational dependence of alanine dipeptide in aqueous solution analyzed with reference interaction site model theory

摘要

With the CHARMM22 (Chemistry at Harvard Macromolecular Mechanics) all-atom nonbonded potential parameters for alanine dipeptide solute and the transferable intermolecular potential model water for the solvent, the reference interaction site model (RISM) integral equations with the hypernetted chain closure are solved to obtain all the atomic solvent-solute radial distribution functions. The solvation structures of alanine dipeptide in its seven conformation: C_(7eq), C_(7aq), C_5, alpha_R, beta, alpha_L and P_(II), in aqueous solution are analyzed at the atomic level in terms of the atomic solute-solvent radial distribution functions. At a temperature of T = 298.15 K and bulk water density rho = 0.9970 g cm~(-3), the corresponding solvation free energies are calcualted by using Singer and Chandler's analytic solvation free energy formulation [Mol. Phys. 55, 621 (1985)]. Solvation energies, enthalpies, and entropies are also calcualted in the RISM theory framework. The solvation thermodynamics for alanine dipeptide in aqueous solution are mainly controlled by the strong hydrophobic groups: CH_3 and CH, which make alanine dipeptide show strong hydrophobicity. But the differences in the solvation thermodynamics for different alanine dipeptide conformers are controlled by the carbonyl groups and amide groups, which make alanine dipeptide show some hydrophilicity and exist in various conformations in aqueous solution. Solvation of alanine dipeptide in aqueous solution is determined by the competition among the molecular packing effects, intramolecular hydrogen bonds, and intermolecualr hydrogen bonds. Due to the intramolecular hydrogen bonds in the two folded C_7 conformations, the two most favorable conformations in gas phase become the least solvated in aqueous solution. Due to the intermolecular hydrogen bonds, C_6, P_(II), alpha_L, alpha_R, and beta become more solvated in aqueous solution.