Kaipeng Zeng

Qitian Wu, Chenxiao Yang, Kaipeng Zeng et al.

The capability of generalization is a cornerstone for the success of modern learning systems. For non-Euclidean data, e.g., graphs, that particularly involves topological structures, one important aspect neglected by prior studies is how machine learning models generalize under topological shifts. This paper proposes Advective Diffusion Transformer (AdvDIFFormer), a physics-inspired graph Transformer model designed to address this challenge. The model is derived from advective diffusion equations which describe a class of continuous message passing process with observed and latent topological structures. We show that AdvDIFFormer has provable capability for controlling generalization error with topological shifts, which in contrast cannot be guaranteed by graph diffusion models, i.e., the generalized formulation of common graph neural networks in continuous space. Empirically, the model demonstrates superiority in various predictive tasks across information networks, molecular screening and protein interactions.

Yu Zhang, Ruijie Yu, Kaipeng Zeng et al.

Identifying reaction conditions that are broadly applicable across diverse substrates is a longstanding challenge in chemical and pharmaceutical research. While many methods are available to generate conditions with acceptable performance, a universal approach for reliably discovering effective conditions during reaction exploration is rare. Consequently, current reaction optimization processes are often labor-intensive, time-consuming, and costly, relying heavily on trial-and-error experimentation. Nowadays, large language models (LLMs) are capable of tackling chemistry-related problems, such as molecule design and chemical reasoning tasks. Here, we report the design, implementation and application of Chemma-RC, a text-augmented multimodal LLM to identify effective conditions through task-specific dialogue and condition generation. Chemma-RC learns a unified representation of chemical reactions by aligning multiple modalities-including text corpus, reaction SMILES, and reaction graphs-within a shared embedding module. Performance benchmarking on datasets showed high precision in identifying optimal conditions, with up to 17% improvement over the current state-of-the-art methods. A palladium-catalysed imidazole C-H arylation reaction was investigated experimentally to evaluate the functionalities of the Chemma-RC in practice. Our findings suggest that Chemma-RC holds significant potential to accelerate high-throughput condition screening in chemical synthesis.

Nianzu Yang, Kaipeng Zeng, Haotian Lu et al.

Neuronal morphology is essential for studying brain functioning and understanding neurodegenerative disorders. As acquiring real-world morphology data is expensive, computational approaches for morphology generation have been studied. Traditional methods heavily rely on expert-set rules and parameter tuning, making it difficult to generalize across different types of morphologies. Recently, MorphVAE was introduced as the sole learning-based method, but its generated morphologies lack plausibility, i.e., they do not appear realistic enough and most of the generated samples are topologically invalid. To fill this gap, this paper proposes MorphGrower, which mimicks the neuron natural growth mechanism for generation. Specifically, MorphGrower generates morphologies layer by layer, with each subsequent layer conditioned on the previously generated structure. During each layer generation, MorphGrower utilizes a pair of sibling branches as the basic generation block and generates branch pairs synchronously. This approach ensures topological validity and allows for fine-grained generation, thereby enhancing the realism of the final generated morphologies. Results on four real-world datasets demonstrate that MorphGrower outperforms MorphVAE by a notable margin. Importantly, the electrophysiological response simulation demonstrates the plausibility of our generated samples from a neuroscience perspective. Our code is available at https://github.com/Thinklab-SJTU/MorphGrower.

Kaipeng Zeng, Xianbin Liu, Yu Zhang et al.

Organic synthesis stands as a cornerstone of the chemical industry. The development of robust machine learning models to support tasks associated with organic reactions is of significant interest. However, current methods rely on hand-crafted features or direct adaptations of model architectures from other domains, which lack feasibility as data scales increase or ignore the rich chemical information inherent in reactions. To address these issues, this paper introduces RAlign, a novel chemical reaction representation learning model for various organic reaction-related tasks. By integrating atomic correspondence between reactants and products, our model discerns the molecular transformations that occur during the reaction, thereby enhancing comprehension of the reaction mechanism. We have designed an adapter structure to incorporate reaction conditions into the chemical reaction representation, allowing the model to handle various reaction conditions and to adapt to various datasets and downstream tasks. Additionally, we introduce a reaction-center-aware attention mechanism that enables the model to concentrate on key functional groups, thereby generating potent representations for chemical reactions. Our model has been evaluated on a range of downstream tasks. Experimental results indicate that our model markedly outperforms existing chemical reaction representation learning architectures on most of the datasets. We plan to open-source the code contingent upon the acceptance of the paper.

Kaipeng Zeng, Bo yang, Xin Zhao et al.

Motivation: Retrosynthesis planning poses a formidable challenge in the organic chemical industry. Single-step retrosynthesis prediction, a crucial step in the planning process, has witnessed a surge in interest in recent years due to advancements in AI for science. Various deep learning-based methods have been proposed for this task in recent years, incorporating diverse levels of additional chemical knowledge dependency. Results: This paper introduces UAlign, a template-free graph-to-sequence pipeline for retrosynthesis prediction. By combining graph neural networks and Transformers, our method can more effectively leverage the inherent graph structure of molecules. Based on the fact that the majority of molecule structures remain unchanged during a chemical reaction, we propose a simple yet effective SMILES alignment technique to facilitate the reuse of unchanged structures for reactant generation. Extensive experiments show that our method substantially outperforms state-of-the-art template-free and semi-template-based approaches. Importantly, our template-free method achieves effectiveness comparable to, or even surpasses, established powerful template-based methods. Scientific contribution: We present a novel graph-to-sequence template-free retrosynthesis prediction pipeline that overcomes the limitations of Transformer-based methods in molecular representation learning and insufficient utilization of chemical information. We propose an unsupervised learning mechanism for establishing product-atom correspondence with reactant SMILES tokens, achieving even better results than supervised SMILES alignment methods. Extensive experiments demonstrate that UAlign significantly outperforms state-of-the-art template-free methods and rivals or surpasses template-based approaches, with up to 5\% (top-5) and 5.4\% (top-10) increased accuracy over the strongest baseline.

Nianzu Yang, Huaijin Wu, Kaipeng Zeng et al.

Machine learning, particularly graph learning, is gaining increasing recognition for its transformative impact across various fields. One such promising application is in the realm of molecule design and discovery, notably within the pharmaceutical industry. Our survey offers a comprehensive overview of state-of-the-art methods in molecule design, particularly focusing on \emph{de novo} drug design, which incorporates (deep) graph learning techniques. We categorize these methods into three distinct groups: \emph{i)} \emph{all-at-once}, \emph{ii)} \emph{fragment-based}, and \emph{iii)} \emph{node-by-node}. Additionally, we introduce some key public datasets and outline the commonly used evaluation metrics for both the generation and optimization of molecules. In the end, we discuss the existing challenges in this field and suggest potential directions for future research.