Electrostatic interactions solvation free energy calculations

Rao and Singh32 calculated relative solvation free energies for normal alkanes, tetra-alkylmethanes, amines and aromatic compounds using AMBER 3.1. Each system was solvated with 216 TIP3P water molecules. The atomic charges were uniformly scaled down by a factor of 0.87 to correct the overestimation of dipole moment by 6-31G basis set. During the perturbation runs, the periodic boundary conditions were applied only for solute-solvent and solvent-solvent interactions with a non-bonded interaction cutoff of 8.5 A. All solute-solute non-bonded interactions were included. Electrostatic decoupling was applied where electrostatic run was completed in 21 windows. Each window included 1 ps of equilibration and 1 ps of data... 

A hybrid approach of the extended scaled particle theory (SPT) and the Poisson-Boltzmann (PB) equation for the solvation free energy of non-polar and polar solutes has been proposed by us. This new method is applied for the hydration free energy of the protein, avian pancreatic polypeptide (36 residues). The contributions form the cavity formation and the attractive interaction between the solute and the solvent to the solvation free energy compensate each other. The electrostatic conffibution is much larger than other terms in this hyelration free energy, because hydrophilic residues are ionized in water. This work is the first step toward further applications of our new method to free energy difference calculation appeared in the stability analysis of protein. 

For the electrostatic component, the free energy varies in a harmonic fashion with respect to deviations from equilibrium with a constant force constant (Figure 11.19). This is a standard result from dielectric theory and means that the mean square fluctuations of the energy on the two surfaces (the second terms in Equation (11.41)) will cancel, leaving just the first term. This leads to a value of for the electrostatic component (i.e. d = 0 5). A simple test of this theory is to calculate the electrostatic contribution to solvation free energies. Here, state X corresponds to the situation where all of the solvent-solvent and intramolecular solute interactions are present but the interaction between the solute and solvent is only described... 

As shown above the size of the explicit water simulations can be rather large, even for a medium sized protein as in the case of the sea raven antifreeze protein (113 amino acid residues and 5391 water). Simulations of that size can require a large amount of computer memory and disk space. If one is interested in the stability of a particular antifreeze protein or in general any protein and not concerned with the protein-solvent interactions, then an alternative method is available. In this case the simulation of a protein in which the explicit waters are represent by a structureless continuum. In this continuum picture the solvent is represented by a dielectric constant. This replacement of the explicit solvent model by a continuum is due to Bom and was initially used to calculate the solvation free energy of ions. For complex systems like proteins one uses the Poisson-Boltzmann equation to solve the continuum electrostatic problem. In... 

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