Crystal Structure Prediction of a Low‐Symmetry Molecular Crystal (P1, Z = Z′ = 1) Using Periodic DFT and Cubic Starting Cells: A Case Study on 1‐{4‐[(prop‐2‐yn‐1‐yl)oxy]phenyl}ethan‐1‐one

Predicting the crystal structure of low‐symmetry molecular crystals without experimental input is a challenging task, especially for systems with space group P1 and a single molecule in the unit cell ( Z = Z′ = 1). In this study, we explore a simple yet effective crystal structure prediction (CSP) strategy using periodic density functional theory (DFT) with the PBE functional and three dispersion corrections—Tkatchenko–Scheffler (TS), Many‐Body Dispersion (MBD * ), and DFT‐D4. As a case study, we investigate 1‐{4‐[(prop‐2‐yn‐1‐yl)oxy]phenyl}ethan‐1‐one, a molecule with four conformations and an experimental crystal structure (CCDC refcode ZOWZAP). Each conformation was placed in a cubic unit cell with varying initial edge lengths and fully optimized in CASTEP using the LBFGS minimizer, allowing simultaneous relaxation of lattice parameters and atomic coordinates. Results show that the choice of dispersion correction and initial cell dimensions critically influences prediction success. The DFT‐D4 method provided the closest agreement with the experimental structure, correctly identifying the experimentally observed conformation as the lowest‐energy arrangement in most cases. The study highlights the feasibility of a minimal‐input CSP workflow for P1 , Z = Z′ = 1 molecular crystals, offering a reproducible approach for systems where experimental diffraction data are unavailable or challenging to obtain.