Improved Polarizable Dipole–Dipole Interaction Model for Hydrogen Bonding, Stacking, T‑Shaped, and X–H···π Interactions

The polarizable dipole–dipole interaction model was formulated in our laboratory to rapidly simulate hydrogen bonding in biosystems. In this paper, this model is improved and further parametrized for stacking, T-shaped, and X–H···π interactions by adding the orbital overlap term and fitting to 19 CCSD­(T)/CBS interaction energy curves of training dimers. The performance of our model is assessed through its application to more than 100 complexes, including hydrogen-bonded, stacked, T-shaped, and X–H···π complexes. For 124 relatively small testing complexes, our model reproduces benchmark equilibrium intermolecular distances with a root-mean-square deviation (RMSD) of 0.08 Å, and it reproduces benchmark interaction energies with a 0.64 kcal/mol RMSD. For 14 large noncovalent complexes, our model reproduces benchmark equilibrium intermolecular distances with a RMSD of 0.05 Å, and it reproduces benchmark interaction energies with a 0.80 kcal/mol RMSD. Extensive comparisons are made to interaction energies calculated via the M06-2X and M06-2X-D3 methods, via the well-known nonpolarizable AMBER99 force field method, via the popular polarizable AMOEBA force field method, and via semiempirical quantum mechanical (SQM) methods. Our statistical evaluations show that our model outperforms the AMBER99, AMOEBA, and SQM methods and is as accurate as the M06-2X and M06-2X-D3 methods. In summary, the model developed in this work is reasonable, and the newly introduced orbital overlap term is effective in the accurate modeling of the noncovalent interactions. Our testing results also indicate that the polarization interaction term is important in the evaluation of hydrogen bonding, whereas the orbital overlap is important in examining short hydrogen bonding, T-shaped, and X–H···π interactions. Our model may serve as a new tool for modeling biological systems where hydrogen bonding, stacking, T-shaped, and X–H···π interactions are of general importance.