Comparing ANI-2x, ANI-1ccx neural networks, force field, and DFT methods for predicting conformational potential energy of organic molecules

Abstract

In this study, the conformational potential energy surfaces of Amylmetacresol, Benzocaine, Dopamine, Betazole, and Betahistine molecules were scanned and analyzed using the neural network architecture ANI-2 × and ANI-1ccx, the force field method OPLS, and density functional theory with the exchange-correlation functional B3LYP and the basis set 6-31G(d). The ANI-1ccx and ANI-2 × methods demonstrated the highest accuracy in predicting torsional energy profiles, effectively capturing the minimum and maximum values of these profiles. Conformational potential energy values calculated by B3LYP and the OPLS force field method differ from those calculated by ANI-1ccx and ANI-2x, which account for non-bonded intramolecular interactions, since the B3LYP functional and OPLS force field weakly consider van der Waals and other intramolecular forces in torsional energy profiles. For a more comprehensive analysis, electronic parameters such as dipole moment, HOMO, and LUMO energies for different torsional angles were calculated at two levels of theory, B3LYP/6-31G(d) and ωB97X/6-31G(d). These calculations confirmed that ANI predictions are more accurate than density functional theory calculations with B3LYP functional and OPLS force field for determining potential energy surfaces. This research successfully addressed the challenges in determining conformational potential energy levels and shows how machine learning and deep neural networks offer a more accurate, cost-effective, and rapid alternative for predicting torsional energy profiles.