Longtao Hu

Di Hu, Kun Li, Haojie Rao et al.

Accurate prediction of molecular properties underpins drug discovery and material design, yet even state-of-the-art models remain vulnerable to localized failure modes that aggregate metrics cannot detect. The places where molecular similarity should be most helpful are also places where standard evaluation can be most misleading. Property cliffs expose this gap: structurally similar molecules can still differ sharply in target property, so models with competitive overall performance may fail in high-risk local neighborhoods. To expose and mitigate this failure mode, CliffSplit, a cliff-aware evaluation protocol that constructs locally supported, cliff-exposed test cases, and CliffLoss, a model-agnostic train-only mitigation mechanism for cliff-sensitive errors, are introduced. Experiments on three QM9 targets and three MoleculeNet tasks across five backbones show that CliffSplit reveals at least 15% higher error in cliff-heavy QM9 regions, while CliffLoss reduces the cliff-to-smooth error gap by up to 30% on Lipophilicity and improves overall MAE by 9.7%. Together, these results turn molecular similarity failure from a descriptive anomaly into a benchmarked evaluation problem for molecular machine learning. The code is available at https://anonymous.4open.science/r/Cliff_Loss.

Kun Li, Longtao Hu, Xiantao Cai et al.

Molecular evolution is the process of simulating the natural evolution of molecules in chemical space to explore potential molecular structures and properties. The relationships between similar molecules are often described through transformations such as adding, deleting, and modifying atoms and chemical bonds, reflecting specific evolutionary paths. Existing molecular representation methods mainly focus on mining data, such as atomic-level structures and chemical bonds directly from the molecules, often overlooking their evolutionary history. Consequently, we aim to explore the possibility of enhancing molecular representations by simulating the evolutionary process. We extract and analyze the changes in the evolutionary pathway and explore combining it with existing molecular representations. Therefore, this paper proposes the molecular evolutionary network (MEvoN) for molecular representations. First, we construct the MEvoN using molecules with a small number of atoms and generate evolutionary paths utilizing similarity calculations. Then, by modeling the atomic-level changes, MEvoN reveals their impact on molecular properties. Experimental results show that the MEvoN-based molecular property prediction method significantly improves the performance of traditional end-to-end algorithms on several molecular datasets. The code is available at https://anonymous.4open.science/r/MEvoN-7416/.

Kun Li, Longtao Hu, Yida Xiong et al.

Molecular representation learning aims to learn vector embeddings that capture molecular structure and geometry, thereby enabling property prediction and downstream scientific applications. In many AI for science tasks, labeled data are expensive to obtain and therefore limited in availability. Under the few-shot setting, models trained with scarce supervision often learn brittle structure-property relationships, resulting in substantially higher prediction errors and reduced generalization to unseen molecules. To address this limitation, we propose PCEvo, a path-consistent representation method that learns from virtual paths through dynamic structural evolution. PCEvo enumerates multiple chemically feasible edit paths between retrieved similar molecular pairs under topological dependency constraints. It transforms the labels of the two molecules into stepwise supervision along each virtual evolutionary path. It introduces a path-consistency objective that enforces prediction invariance across alternative paths connecting the same two molecules. Comprehensive experiments on the QM9 and MoleculeNet datasets demonstrate that PCEvo substantially improves the few-shot generalization performance of baseline methods. The code is available at https://anonymous.4open.science/r/PCEvo-4BF2.

Kun Li, Zhennan Wu, Yida Xiong et al.

Drug discovery is of great social significance in safeguarding human health, prolonging life, and addressing the challenges of major diseases. In recent years, artificial intelligence has demonstrated remarkable advantages in key tasks across bioinformatics and pharmacology, owing to its efficient data processing and data representation capabilities. However, most existing computational platforms cover only a subset of core tasks, leading to fragmented workflows and low efficiency. In addition, they often lack algorithmic innovation and show poor generalization to out-of-distribution (OOD) data, which greatly hinders the progress of drug discovery. To address these limitations, we propose Baishenglai (BSL), a deep learning-enhanced, open-access platform designed for virtual drug discovery. BSL integrates seven core tasks within a unified and modular framework, incorporating advanced technologies such as generative models and graph neural networks. In addition to achieving state-of-the-art (SOTA) performance on multiple benchmark datasets, the platform emphasizes evaluation mechanisms that focus on generalization to OOD molecular structures. Comparative experiments with existing platforms and baseline methods demonstrate that BSL provides a comprehensive, scalable, and effective solution for virtual drug discovery, offering both algorithmic innovation and high-precision prediction for real-world pharmaceutical research. In addition, BSL demonstrated its practical utility by discovering novel modulators of the GluN1/GluN3A NMDA receptor, successfully identifying three compounds with clear bioactivity in in-vitro electrophysiological assays. These results highlight BSL as a promising and comprehensive platform for accelerating biomedical research and drug discovery. The platform is accessible at https://www.baishenglai.net.