Accurate determination of solvation free energies of neutral organic compounds from first principles

• Published in: Nature communications 2022-01, Vol.13 (1), p.414-414, Article 414
• Main Authors: Pereyaslavets, Leonid, Kamath, Ganesh, Butin, Oleg, Illarionov, Alexey, Olevanov, Michael, Kurnikov, Igor, Sakipov, Serzhan, Leontyev, Igor, Voronina, Ekaterina, Gannon, Tyler, Nawrocki, Grzegorz, Darkhovskiy, Mikhail, Ivahnenko, Ilya, Kostikov, Alexander, Scaranto, Jessica, Kurnikova, Maria G., Banik, Suvo, Chan, Henry, Sternberg, Michael G., Sankaranarayanan, Subramanian K. R. S., Crawford, Brad, Potoff, Jeffrey, Levitt, Michael, Kornberg, Roger D., Fain, Boris
• Format: Article
• Language: English
• Subjects: 119/118; 639/638/563/606; 639/638/563/758; 639/638/563/981; computational chemistry; Computer applications; Cyclohexane; First principles; Free energy; Humanities and Social Sciences; INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; Liquid phases; Model accuracy; molecular dynamics; Molecular modelling; multidisciplinary; Organic chemistry; Organic compounds; quantum chemistry; Room temperature; Science; Science (multidisciplinary); Simulation; Software; Solvation
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-28041-0

The main goal of molecular simulation is to accurately predict experimental observables of molecular systems. Another long-standing goal is to devise models for arbitrary neutral organic molecules with little or no reliance on experimental data. While separately these goals have been met to various degrees, for an arbitrary system of molecules they have not been achieved simultaneously. For biophysical ensembles that exist at room temperature and pressure, and where the entropic contributions are on par with interaction strengths, it is the free energies that are both most important and most difficult to predict. We compute the free energies of solvation for a diverse set of neutral organic compounds using a polarizable force field fitted entirely to ab initio calculations. The mean absolute errors (MAE) of hydration, cyclohexane solvation, and corresponding partition coefficients are 0.2 kcal/mol, 0.3 kcal/mol and 0.22 log units, i.e . within chemical accuracy. The model (ARROW FF) is multipolar, polarizable, and its accompanying simulation stack includes nuclear quantum effects (NQE). The simulation tools’ computational efficiency is on a par with current state-of-the-art packages. The construction of a wide-coverage molecular modelling toolset from first principles, together with its excellent predictive ability in the liquid phase is a major advance in biomolecular simulation. Theoretical estimations of solvation free energy by continuum solvation models are generally not accurate. Here the authors report a polarizable force field fitted entirely to first-principles calculations for the estimation of free energy of solvation of arbitrary molecules.