Energy–Entropy Compensation in the Transfer of Nonpolar Solutes from Water to Cosolvent/Water Mixtures

Biomolecular Modeling: Goals, Problems, Perspectives

“…[144][145][146] This is illustrated in Figure 11, where the number of conformations visited during a MD simulation of a polypeptide and of another polymer of equal length are shown. This number grows sublinearly for the b-heptapeptide in methanol and levels off at about 200 conformations (Figure 11 A), whereas the number of visited (relevant) conformations for a poly(hydroxybutanoate) molecule of similar length in chloroform grows linearly with time (Figure 11 B), as would be expected considering the number of possible conformations for either molecule is about 10 9 . The difference is due to the presence of hydrogen-bond donor and acceptor atoms in the b-heptapeptide, which restrict (through favorable hydrogen bonding) the conformational space accessible to the molecule Figure 11.…”

“…The thermodynamic properties, such as energy and density of mixing, are of particular importance when the free energy of solvation and folding of solutes is to be calculated. [8,9,[41][42][43] The properties of a mixture of two solvents need not be a linear function of its composition, as illustrated for water/ dimethyl sulfoxide (DMSO) mixtures in Figure 9. Only the dielectric permittivity e shows a linear behavior, while the other properties considered show different types of nonlinearity.…”

“…Changes in free energy that drive processes may result from changes in internal energy (U) or in entropy (S), which may work together or against each other depending on the relative strengths of the nonbonded interactions between the various components (atoms, molecules) of the system. [8,9] Figure 4 illustrates the phenomenon of energy-entropy compensation: two conformations x 1 and x 2 of a molecule may have U(x 1 ) ! U(x 2 ), while F(x 1 ) > F(x 2 ) if at a given temperature S(x 1 ) !…”

“…The hydrogen bonds charac- ] for solute transfer from pure water to co-solvent/water mixtures at 298 K and 1 atm as calculated from MD simulations. [9] Mole fractions are given in percent. Two different models (I and II) were used for acetone.…”

Estimating entropies from molecular dynamics simulations

“…For processes in which the solvent-solvent energy/enthalpy term is nearly constant, the solute-solvent energy/enthalpy and entropy terms will be representative for for the total energy and entropy terms, respectively. For example, 40,41 the relative contributions of enthalpy and entropy to the free enthalpy of solvation of a series of small solutes in different binary and ternary aqueous solutions could be understood using the solute-solvent energy and entropy terms investigated here. The one-step perturbation approach is a poor approximation to determine entropy differences, even when using it to estimate an entropy difference through determination of the temperature dependence of the corresponding free-energy difference.…”