New solvation free energy function comprising intermolecular solvation and intramolecular self-solvation terms

Abstract

Solvation free energy is a fundamental thermodynamic quantity that should be determined to estimate various physicochemical properties of a molecule and the desolvation cost for its binding to macromolecular receptors. Here, we propose a new solvation free energy function through the improvement of the solvent-contact model, and test its applicability in estimating the solvation free energies of organic molecules with varying sizes and shapes. This new solvation free energy function is constructed by combining the existing solute-solvent interaction term with the self-solvation term that reflects the effects of intramolecular interactions on solvation. Four kinds of atomic parameters should be determined in this solvation model: atomic fragmental volume, maximum atomic occupancy, atomic solvation, and atomic self-solvation parameters. All of these parameters for total 37 atom types are optimized by the operation of a standard genetic algorithm in such a way to minimize the difference between the experimental solvation free energies and those calculated by the solvation free energy function for 362 organic molecules. The solvation free energies estimated from the new solvation model compare well with the experimental results with the associated squared correlation coefficients of 0.88 and 0.85 for training and test sets, respectively. The present solvation model is thus expected to be useful for estimating the solvation free energies of organic molecules.

Experimental and theoretical studies on the molecular properties of ciprofloxacin, norfloxacin, pefloxacin, sparfloxacin, and gatifloxacin in determining bioavailability

“…In drug design, it is the n -octanol-water partition coefficient, log P o/w , which is commonly used as the standard lipophilicity parameter [8]. P o/w is directly related to the free energy of binding [9, 10]. P o/w is an equilibrium constant for solute transfer between octanol and water, as evidenced by the following equation:where T is the absolute temperature, R the gas constant, and ΔG° the binding free energy variation measured under standard conditions (298 K, 1 atm, and 1 M concentration for both reagents and products).…”

Discovery of Novel DUSP16 Phosphatase Inhibitors through Virtual Screening with Homology Modeled Protein Structure

“…23 This modification of the scoring function seems to increase the accuracy in virtual screening of DUSP16 inhibitors because the underestimation of ligand solvation often leads to the overestimation of the binding affinity of an inhibitor with many polar atoms. Indeed, the superiority of this modified scoring function to the previous one was well appreciated in recent studies for virtual screening of kinase and phosphatase inhibitors.…”

Computational prediction of octanol–water partition coefficient based on the extended solvent-contact model

“…Because V i parameters exhibited a bad convergent behavior in the simultaneous optimization of three kinds of atomic parameters, they were optimized separately with a standard genetic algorithm as detailed in our previous papers [18,19]. The S i and O i,max parameters of each atom type were then optimized through the standard genetic algorithm to make the solvation free energy functions complete.…”

“…(2), we define the molecular solvation free energy functions in the two solvents based on the solvent-contact model [16,17]. As detailed in our previous papers on the extended solvent-contact model [18,19], the solvation free energy of a molecule can be obtained with the interatomic distances (r ij 's) between solute atoms and the three atomic parameters. …”