Benchmarking binding energy calculations for organic structure-directing agents in pure-silica zeolites.

Molecular modeling plays an important role in the discovery of organic structure-directing agents (OSDAs) for zeolites. By quantifying the intensity of host-guest interactions, it is possible to select cost-effective molecules that maximize binding toward a given zeolite framework. Over the last few decades, a variety of methods and levels of theory have been used to calculate these binding energies. Nevertheless, there is no consensus on the best calculation strategy for high-throughput virtual screening undertakings. In this work, we compare binding affinities from density functional theory (DFT) and Dreiding force field calculations for 272 zeolite-OSDA pairs obtained from static and time-averaged simulations. Enabled by automation software, we show that Dreiding binding energies from the frozen pose method correlate best with DFT energies. They are also less sensitive to the choice of initial lattice parameters and optimization algorithms, as well as less computationally expensive than their time-averaged counterparts. Furthermore, we demonstrate that a broader exploration of the conformation space from molecular dynamics simulations does not provide significant improvements in binding energy trends over the frozen pose method despite being orders of magnitude more expensive. The code and benchmark data are open-sourced and provide robust and computationally efficient guidelines to calculating binding energies in zeolite-OSDA pairs.