Effects of Polarizable Solvent Models upon the Relative Stability of an α-Helical and a β-Hairpin Structure of an Alanine Decapeptide

Abstract

The free enthalpy of changing a nonpolarizable solvent into a polarizable solvent is calculated for an alanine decapeptide solvated in water, methanol, chloroform, or carbon tetrachloride. Introducing polarizability into a water solvent does not change the relative stability between the α-helix and the β-hairpin, while for methanol and chloroform the α-helix is stabilized by about 1 kJ mol(-1) per residue and for carbon tetrachloride by about 2 kJ mol(-1) per residue. These results suggest that the less polar the solvent is, the more the α-helical structure is stabilized with respect to the β-hairpin structure by the use of a polarizable solvent model instead of a nonpolarizable one. This highlights that inclusion of polarizability in models for less polar and nonpolar solvents or protein environments is as important as, if not more important than, including polarizability in models for liquid water.

Polarizable Force Fields for Biomolecular Simulations: Recent Advances and Applications

“…This highlights that inclusion of polarizability in models for less polar and nonpolar solvents or protein environments is as important as including polarizability in models for liquid water. (63) Additionally, an MD study of alkali-acetate solutions at various concentrations indicated that polarizable force fields may be needed to accurately capture behavior of protein in electrolyte solutions using MD simulations. (1) Protein-Ion and Protein-Ligand Binding Several recent studies have been focused on capturing the interactions of ions with proteins and nucleic acids.…”

Effects of a More Accurate Polarizable Hamiltonian on Polymorph Free Energies Computed Efficiently by Reweighting Point-Charge Potentials

“…Potentials with polarizability are better able to account for anisotropic or polar environments and have been shown to be critical when calculating free energies of binding and solvation in solutions. [54][55][56][57][58] The inclusion of polarization is likely to be even more important in periodic solids due to long-range electrostatic correla-3 tions, and numerous crystallographic studies based on lattice energies have emphasized the need for distributed multipoles or full polarization for proper polymorph prediction. 6,23,25,32,33,36,[59][60][61][62][63][64][65] For example, Williams and Weller modeled various azabenzene structures and concluded that no point-charge model will be able to reproduce the correct structures unless additional lone pair sites are included.…”

Energetics and J-coupling constants for Ala, Gly, and Val peptides demonstrated using ABEEM polarizable force field in vacuo and an aqueous solution

“…In addition to the flexibility of the conformation of amino acids, the interactions between the solute and solvent are also essential for determining the conformations using MD simulations. 110,111 In this work, the energetics of Ala, Gly, Val dipeptides and tripeptides were explored using the ABEEM PFF method together with the AMBER99sb, OPLS/AA, and CHARMM fixedcharge FF, and AMOEBA PFF methods, which were then compared with the results obtained using ab initio methods in vacuo. The good agreement observed for the minimum location, energy order of the minima, and each atomic charge with the ab initio method are beneficial for fitting the fluctuating charge and torsional functions.…”