Calculation of the aqueous solvation energy and entropy, as well as free energy, of simple polar solutes

Abstract

With the advent of more powerful computers, the question of calculating thermodynamic quantities, such as the energy and the entropy, in solute-solvent systems is revisited. The calculation of these thermodynamic quantitites was limited in the past by their slow convergence relative to the free energy. Using molecular dynamics simulations, the energy, entropy, and free energy of solvation of NMA and CH(3)NH(2), as well as their relative values, have been determined. Three different methods (the thermodynamic perturbation method, the thermodynamic integration method, and a finite-difference method) are compared. The finite difference method gives the best results and accurate values for the entropy and energy were obtained using a reasonable amount to computer time. The results suggest that a meaningful thermodynamic description of biomolecular processes can be realized with present methods and the available computer time.

Refining the description of peptide backbone conformations improves protein simulations using the GROMOS 53A6 force field

“…This probably happens because of the united atom descriptions of the two methyl groups with zero partial charges, rather than because of the problems modeling the charge distributions of the peptide groups. The dipole moment of the NMA model with off-center charges (4.38 D) has been purposefully kept almost unchanged when compared with the original GROMOS 53A6 values (4.14 D), similar to the reported experimental values of 4.39 D. 54 Solvation free energies of NMA have been reported using other biomolecular force field, some underestimation when compared with experimental results have also been reported except for CHARMM (232.87 kJ mol 21 for OPLS, 59 247.26 kJ mol 21 for CHARMM, 60 and 237.2 kJ mol 21 for AMBER 61 ). All these studies have employed all-atom models and significant amount of partial charges have been assigned on atoms of the methyl groups.…”

Will molecular dynamics simulations of proteins ever reach equilibrium?

“…30,31,32,33 Many different methods to calculate entropies from MD simulations have been proposed 8,9,10,11,12,13,14,15 and they have been evaluated previously several times, but mainly for rather simple and small systems. 12,13,14,34,35 In this article, we perform a detailed analysis of five different protein or protein-ligand systems.…”

Atomic hydration potentials using a Monte Carlo Reference State (MCRS) for protein solvation modeling

“…Interestingly, while Molecular Dynamics simulation of pure liquid water reproduces well the experimental radial distribution function (and other physical properties) in water [48] and simple solutions [49], the same function of radial oxygen-oxygen contact frequency, obtained during MD simulation of solvated protein crystals, may have maxima locations and amplitudes different from those obtained for pure water [1]. …”