Revisiting the Potential Energy Surface of the Stacked Cytosine Dimer: FNO-CCSD(T) Interaction Energies, SAPT Decompositions, and Benchmarking

Abstract

Nucleobase stacking interactions are crucial for the stability of nucleic acids. This study investigates base stacking energies of the cytosine homodimer in different configurations, including intermolecular separation plots, detailed twist dependence, and displaced structures. Highly accurate ab initio quantum chemical single point energies using an energy function based on MP2 complete basis set extrapolation ([6 → 7]ZaPa-NR) and a CCSD(T)/cc-pVTZ-F12 high-level correction are presented as new reference data, providing the most accurate stacking energies of nucleobase dimers currently available. Accurate SAPT2+(3)δMP2 energy decomposition is used to obtain detailed insights into the nature of base stacking interactions at varying vertical distances and twist values. The ab initio symmetry adapted perturbation theory (SAPT) energy decomposition suggests that the base stacking originates from an intricate interplay between dispersion attraction, short-range exchange-repulsion, and Coulomb interaction. The interpretation of the SAPT data is a complex issue as key energy terms vary substantially in the region of optimal (low energy) base stacking geometries. Thus, attempts to highlight one leading stabilizing SAPT base stacking term may be misleading and the outcome strongly depends on the used geometries within the range of geometries sampled in nucleic acids upon thermal fluctuations. Modern dispersion-corrected density functional theory (among them DSD-BLYP-D3, ωB97M-V, and ωB97M-D3BJ) is benchmarked and often reaches up to spectroscopic accuracy (below 1 kJ/mol). The classical AMBER force field is benchmarked with multiple different sets of point-charges (e.g. HF, DFT, and MP2-based) and is found to produce reasonable agreement with the benchmark data.