Efficient Molecular Crystal Structure Prediction and Stability Assessment with AIMNet2 Neural Network Potentials

Identifying thermodynamically stable crystal structures remains a key challenge in materials chemistry. Computational crystal structure prediction (CSP) workflows typically rank candidate structures by lattice energy to assess relative stability. Approaches using self-consistent first-principles calculations become prohibitively expensive, especially when millions of energy evaluations are required for complex molecular systems with many atoms per unit cell. Here, we provide a detailed analysis of our methodology and results from the seventh blind test of crystal structure prediction organized by the Cambridge Crystallographic Data Centre (CCDC). We present an approach that significantly accelerates CSP by training target-specific machine-learned interatomic potentials (MLIPs). AIMNet2 MLIPs are trained on density functional theory (DFT) calculations of molecular clusters, herein referred to as <i>n</i>-mers. We demonstrate that potentials trained on gas phase dispersion-corrected DFT reference data of <i>n</i>-mers successfully extend to crystalline environments, accurately characterizing the CSP landscape and correctly ranking structures by relative stability. Our methodology effectively captures the underlying physics of thermodynamic crystal stability using only molecular cluster data, avoiding the need for expensive periodic calculations. The performance of target-specific AIMNet2 interatomic potentials is illustrated across diverse chemical systems relevant to pharmaceutical, optoelectronic, and agrochemical applications, demonstrating their promise as efficient alternatives to full DFT calculations for routine CSP tasks.