MōLe-Λ: Learning the Coupled-Cluster Response State for Energies, Gradients, and Properties

Large language models (LLMs) are widely applied across chemical tasks, such as molecular property prediction, which underpins drug discovery. Molecular LLMs represent a molecule through several modalities, notably a 1D SMILES sequence or a 2D molecular graph. Both encode molecular information implicitly, so the contribution of individual substructures remains opaque. Retrieval and augmentation methods add context, but from external sources. However, the cues chemists reason over are the internal substructures that drive a property up or down. We propose MR-MoL, a multi-granular rationale-guided molecular LLM that supplies this evidence directly. A fine-tuned GNN scores each substructure through masking, and the most influential ones are serialized as a ranked, direction-tagged rationale that the LLM reads alongside the SMILES sequence and molecular graph. The rationale spans three levels of granularity: Murcko scaffolds with their side chains, BRICS fragments, and functional groups. This is, to our knowledge, the first method to expose GNN-derived attributions to an LLM as evidence for property prediction. On eight MoleculeNet tasks, MR-MoL achieves the best overall results among generalist models and narrows the gap to specialist models tuned for each task. Five diagnostics further confirm that the model reads the rationale rather than merely benefiting from its presence. Its direction, rank, and substructure each shape the prediction, and its attributions reproduce known structure-property relationships.

Machine learning interatomic potentials (MLIPs) require generating computationally expensive, large-scale training datasets to accurately simulate materials and molecules. Incorporating electronic structure information using multitask learning improves sample efficiency, however, training on full Hamiltonian matrices, which scale quadratically with the number of atoms, is intractable for large datasets. In this work, we show that multitask learning utilizing orbitally resolved semiempirical charges significantly improves sample efficiency and accuracy in MLIPs. To efficiently predict orbital charges, we implement a specialized equivariant model, reducing charge prediction error compared to an invariant baseline. By augmenting training with computationally inexpensive GFN1-xTB orbital charges, which scale linearly with the number of atoms, our model achieves a 46% reduction in energy mean absolute error and requires five times less data to match the performance of energy-only models. Furthermore, our approach outperforms models trained on expensive density functional theory (DFT) atomic charges, capturing orbitally resolved electronic complexity and forcing the network to learn a physically accurate latent space that spontaneously clusters metals by shared chemical properties. Because orbital charges are only required during training, this approach preserves inference efficiency, providing a scalable recipe for developing accurate, data-efficient foundation models for complex chemical systems.

Advances in deep learning architectures and representations have enabled ML-driven chemical property prediction, but state-of-the-art (SOTA) models have remained largely confined to independent codebases and lack support for diverse chemical species. This work introduces ElemeNet, a unified, general-purpose software package for molecular machine learning. The ElemeNet software package enables the training of advanced ML models for diverse properties and datasets with an enlarged range of elemental compositions. We define molecular representations compatible with elements 1-100, supporting diverse organometallic and biological systems in addition to organic chemistry already well-served by the Chemprop ML toolkit. As well as more common atom-, bond-, and molecule-level predictions, we introduce moiety predictions. We also natively define optional conditioning on charge and spin states. Advanced E(3)-equivariant and transformer architectures are supported, as well as classical 2D models, with all classes including built-in uncertainty quantification through deterministic and statistical measures. We benchmark our protocols for ML model training against representative datasets from organic, inorganic, coordination, and biological chemistry, achieving competitive and SOTA performance relative to literature baselines and favorable scaling to millions of molecules. The entire workflow is exposed through a concise command-line interface, lowering the barrier to entry for non-expert users. We anticipate ElemeNet will empower non-computational researchers to leverage modern deep learning methods across the chemical and physical sciences.