Metz, Michael P.Shahbaz, MuhammadSong, HongxingVogt-Maranto, LeslieTuckerman, Mark E.Szalewicz, Krzysztof2022-03-162022-03-162022-01-24Metz, Michael P., Muhammad Shahbaz, Hongxing Song, Leslie Vogt-Maranto, Mark E. Tuckerman, and Krzysztof Szalewicz. “Crystal Structure Predictions for 4-Amino-2,3,6-Trinitrophenol Using a Tailor-Made First-Principles-Based Force Field.” Crystal Growth & Design 22, no. 2: 1182–95. https://doi.org/10.1021/acs.cgd.1c01117.1528-7505https://udspace.udel.edu/handle/19716/30667This document is the Accepted Manuscript version of a Published Work that appeared in final form in Crystal Growth and Design, copyright 2022 American Chemical Society. To access the final edited and published work see https://doi.org/10.1021/acs.cgd.1c01117. This article will be embargoed until 01/24/2023.Predictions of crystal structures from first-principles electronic structure calculations and molecular simulations have been performed for an energetic molecule, 4-amino-2,3,6-trinitrophenol. This physics-based approach consists of a series of steps. First, a tailor-made two-body potential energy surface (PES) was constructed with recently developed software, autoPES, using symmetry-adapted perturbation theory based on a density-functional theory description of monomers [SAPT(DFT)]. The fitting procedure ensures asymptotic correctness of the PES by employing a rigorous asymptotic multipole expansion, which seamlessly integrates with SAPT(DFT) interaction energies. Next, crystal structure prediction (CSP) was performed by generating possible crystal structures with rigid molecules, minimizing these structures using the SAPT(DFT) force field, and running isothermal–isobaric molecular dynamics (MD) simulations with flexible molecules based on the tailor-made SAPT(DFT) intermolecular force field and a generic/SAPT(DFT) intramolecular one. This workflow led to the experimentally observed structure being identified as one of the forms with the lowest lattice energy, demonstrating the success of a first-principles, bottom-up approach to CSP. Importantly, we argue that the accuracy of the intermolecular potential, here the SAPT(DFT)-based potential, is determinative of the crystal structure, while generic/SAPT(DFT) force fields can be used to represent the intramolecular potential. This force field approach simplifies the CSP workflow, without significantly compromising the accuracy of the prediction.en-USArticle