Characterizing molecular solvation free energy with an efficient density functional theory formalism

Knowledge of solvation free energy or chemical potential of a molecular or macromolecular solute immersed in a molecular solvent like water is the starting point of many applications in different fields. Numerical theories making predictions in limited restitution time lack efficient solution of the molecular Ornstein-Zernike (MOZ) equation in the integral equation (IE) or classical molecular density functional theory (MDFT) formalisms. A group of experimental and theoretical chemists from CEA, CNRS, Université Paris-Saclay, PSL Research University and Sorbonne Universités overcome this limitation using generalized spherical harmonics expansions. They report this work in The Journal of Chemical Physics.

Within the 3D-MDFT and MOZ approaches, the authors investigated the molecular solvent density functional F [ρ (r, Ω)] in the hypernetted chain approximation that considers the 3D absolute position r and the orientation within a fixed laboratory frame Ω (three Euler angles) of the rigid solvent molecules around a solute of arbitrary complexity. The authors then applied a method to overcome angular convolution, the main barrier to efficient resolution, using expansions onto generalized spherical harmonics and moving back and forth between fixed laboratory and local molecular frames.

To assess the numerical efficiency of their formalism, the researchers computed the solvation free energy of a pyrimidine molecule dissolved in water and the solvent density profile around a protein. Overall, they found their formalism increased efficiency by several orders of magnitude compared to previous angular convolution approaches.

In the article, the authors explain that, moving forward, their formalism’s efficiency could potentially compete with numerical simulations and characterize solvation and binding for larger amounts of multi-sized molecular solutes. Coauthor Luc Belloni says, “We may be close to producing a valuable tool for the virtual screening and docking at the heart of drug discovery.”

Source: “Efficient molecular density functional theory using generalized spherical harmonics expansions,” by Lu Ding, Maximilien Levesque, Daniel Borgis, and Luc Belloni, The Journal of Chemical Physics (2017). The article can be accessed at https://doi.org/10.1063/1.4994281 .