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Collaborating Authors

 Ma, Jianzhu


A Neural Symbolic Model for Space Physics

arXiv.org Artificial Intelligence

In this study, we unveil a new AI model, termed PhyE2E, to discover physical formulas through symbolic regression. PhyE2E simplifies symbolic regression by decomposing it into sub-problems using the second-order derivatives of an oracle neural network, and employs a transformer model to translate data into symbolic formulas in an end-to-end manner. The resulting formulas are refined through Monte-Carlo Tree Search and Genetic Programming. We leverage a large language model to synthesize extensive symbolic expressions resembling real physics, and train the model to recover these formulas directly from data. A comprehensive evaluation reveals that PhyE2E outperforms existing state-of-the-art approaches, delivering superior symbolic accuracy, precision in data fitting, and consistency in physical units. We deployed PhyE2E to five applications in space physics, including the prediction of sunspot numbers, solar rotational angular velocity, emission line contribution functions, near-Earth plasma pressure, and lunar-tide plasma signals. The physical formulas generated by AI demonstrate a high degree of accuracy in fitting the experimental data from satellites and astronomical telescopes. We have successfully upgraded the formula proposed by NASA in 1993 regarding solar activity, and for the first time, provided the explanations for the long cycle of solar activity in an explicit form. We also found that the decay of near-Earth plasma pressure is proportional to r^2 to Earth, where subsequent mathematical derivations are consistent with satellite data from another independent study. Moreover, we found physical formulas that can describe the relationships between emission lines in the extreme ultraviolet spectrum of the Sun, temperatures, electron densities, and magnetic fields. The formula obtained is consistent with the properties that physicists had previously hypothesized it should possess.


Integrating Protein Dynamics into Structure-Based Drug Design via Full-Atom Stochastic Flows

arXiv.org Artificial Intelligence

The dynamic nature of proteins, influenced by ligand interactions, is essential for comprehending protein function and progressing drug discovery. Traditional structure-based drug design (SBDD) approaches typically target binding sites with rigid structures, limiting their practical application in drug development. While molecular dynamics simulation can theoretically capture all the biologically relevant conformations, the transition rate is dictated by the intrinsic energy barrier between them, making the sampling process computationally expensive. To overcome the aforementioned challenges, we propose to use generative modeling for SBDD considering conformational changes of protein pockets. We curate a dataset of apo and multiple holo states of protein-ligand complexes, simulated by molecular dynamics, and propose a full-atom flow model (and a stochastic version), named DynamicFlow, that learns to transform apo pockets and noisy ligands into holo pockets and corresponding 3D ligand molecules. Additionally, the resultant holo-like states provide superior inputs for traditional SBDD approaches, playing a significant role in practical drug discovery. Modern deep learning is advancing several areas within drug discovery. Notably, among these, structure-based drug design (SBDD) (Anderson, 2003) emerges as a particularly significant and challenging domain. SBDD aims to discover drug-like ligand molecules specifically tailored to target binding sites. However, the complexity of chemical space and the dynamic nature of molecule conformations make traditional methods such as high throughput and virtual screenings inefficient. Additionally, relying on compound databases limits the diversity of identified molecules. Thus, deep generative models, such as autoregressive models (Luo et al., 2021; Peng et al., 2022) and diffusion models (Guan et al., 2023; Schneuing et al., 2022), have been introduced as a tool for de novo 3D ligand molecule design based on binding pockets, significantly transforming research paradigms. However, most SBDD methods based on deep generative models assume that proteins are rigid (Peng et al., 2022; Guan et al., 2024). However, the dynamic behavior of proteins is crucial for practical drug discovery (Karelina et al., 2023; Boehr et al., 2009). Thermodynamic fluctuations result in proteins existing as an ensemble of various conformational states, and such states may interact with different drug molecules. During binding, the protein's structure may undergo fine-tuning, adopting different conformations to optimize its interaction with the drug, a phenomenon referred to as induced fit (Sherman et al., 2006).


MatterChat: A Multi-Modal LLM for Material Science

arXiv.org Artificial Intelligence

In-silico material discovery and design have traditionally relied on high-fidelity first-principles methods such as density functional theory (DFT) [1] and ab-initio molecular dynamics (AIMD) [2] to accurately model atomic interactions and predict material properties. Despite their effectiveness, these methods face significant challenges due to their prohibitive computational cost, limiting their scalability for highthroughput screening across vast chemical spaces and for simulations over large length and time scales. Moreover, many advanced materials remain beyond the reach of widespread predictive theories due to a fundamental lack of mechanistic understanding. These challenges stem from the inherent complexity of their chemical composition, phase stability, and the intricate interplay of multiple order parameters, compounded by the lack of self-consistent integration between theoretical models and multi-modal experimental findings. As a result, breakthroughs in functional materials, such as new classes of correlated oxides, nitrides, and low-dimensional quantum materials, have largely been serendipitous or guided by phenomenological intuition rather than systematic, theory-driven design. Attempts to predict new materials and functionalities have often led to mixed results, with theoretically proposed systems failing to exhibit the desired properties when synthesized and tested.


Data Mining in Transportation Networks with Graph Neural Networks: A Review and Outlook

arXiv.org Artificial Intelligence

Data mining in transportation networks (DMTNs) refers to using diverse types of spatio-temporal data for various transportation tasks, including pattern analysis, traffic prediction, and traffic controls. Graph neural networks (GNNs) are essential in many DMTN problems due to their capability to represent spatial correlations between entities. Between 2016 and 2024, the notable applications of GNNs in DMTNs have extended to multiple fields such as traffic prediction and operation. However, existing reviews have primarily focused on traffic prediction tasks. To fill this gap, this study provides a timely and insightful summary of GNNs in DMTNs, highlighting new progress in prediction and operation from academic and industry perspectives since 2023. First, we present and analyze various DMTN problems, followed by classical and recent GNN models. Second, we delve into key works in three areas: (1) traffic prediction, (2) traffic operation, and (3) industry involvement, such as Google Maps, Amap, and Baidu Maps. Along these directions, we discuss new research opportunities based on the significance of transportation problems and data availability. Finally, we compile resources such as data, code, and other learning materials to foster interdisciplinary communication. This review, driven by recent trends in GNNs in DMTN studies since 2023, could democratize abundant datasets and efficient GNN methods for various transportation problems including prediction and operation.


Group Ligands Docking to Protein Pockets

arXiv.org Artificial Intelligence

Molecular docking is a key task in computational biology that has attracted increasing interest from the machine learning community. While existing methods have achieved success, they generally treat each protein-ligand pair in isolation. Inspired by the biochemical observation that ligands binding to the same target protein tend to adopt similar poses, we propose \textsc{GroupBind}, a novel molecular docking framework that simultaneously considers multiple ligands docking to a protein. This is achieved by introducing an interaction layer for the group of ligands and a triangle attention module for embedding protein-ligand and group-ligand pairs. By integrating our approach with diffusion-based docking model, we set a new S performance on the PDBBind blind docking benchmark, demonstrating the effectiveness of our proposed molecular docking paradigm.


TFG-Flow: Training-free Guidance in Multimodal Generative Flow

arXiv.org Artificial Intelligence

Given an unconditional generative model and a predictor for a target property (e.g., a classifier), the goal of training-free guidance is to generate samples with desirable target properties without additional training. As a highly efficient technique for steering generative models toward flexible outcomes, training-free guidance has gained increasing attention in diffusion models. However, existing methods only handle data in continuous spaces, while many scientific applications involve both continuous and discrete data (referred to as multimodality). Another emerging trend is the growing use of the simple and general flow matching framework in building generative foundation models, where guided generation remains under-explored. To address this, we introduce TFG-Flow, a novel training-free guidance method for multimodal generative flow. TFG-Flow addresses the curse-of-dimensionality while maintaining the property of unbiased sampling in guiding discrete variables. We validate TFG-Flow on four molecular design tasks and show that TFG-Flow has great potential in drug design by generating molecules with desired properties. Recent advancements in generative foundation models have demonstrated their increasing power across a wide range of domains (Reid et al., 2024; Achiam et al., 2023; Abramson et al., 2024). In particular, diffusion-based foundation models, such as Stable Diffusion (Esser et al., 2024) and SORA (Brooks et al., 2024) have achieved significant success, catalyzing a new wave of applications in areas such as art and science. As these models become more prevalent, a critical question arises: how can we steer these foundation models to achieve specific properties during inference time? One promising direction is using classifier-based guidance (Dhariwal & Nichol, 2021) or classifierfree guidance (Ho & Salimans, 2022), which typically necessitate training a specialized model for each conditioning signal (e.g., a noise-conditional classifier or a text-conditional denoiser). This resource-intensive and time-consuming process greatly limits their applicability. Recently, there has been growing interest in training-free guidance for diffusion models, which allows users to steer the generation process using an off-the-shelf differentiable target predictor without requiring additional model training (Ye et al., 2024). A target predictor can be any classifier, loss, or energy function used to score the quality of the generated samples. Training-free guidance offers a flexible and efficient means of customizing generation, holding the potential to transform the field of generative AI.


Geometric Point Attention Transformer for 3D Shape Reassembly

arXiv.org Artificial Intelligence

Shape assembly, which aims to reassemble separate parts into a complete object, has gained significant interest in recent years. Existing methods primarily rely on networks to predict the poses of individual parts, but often fail to effectively capture the geometric interactions between the parts and their poses. In this paper, we present the Geometric Point Attention Transformer (GPAT), a network specifically designed to address the challenges of reasoning about geometric relationships. In the geometric point attention module, we integrate both global shape information and local pairwise geometric features, along with poses represented as rotation and translation vectors for each part. To enable iterative updates and dynamic reasoning, we introduce a geometric recycling scheme, where each prediction is fed into the next iteration for refinement. We evaluate our model on both the semantic and geometric assembly tasks, showing that it outperforms previous methods in absolute pose estimation, achieving accurate pose predictions and high alignment accuracy.


Hotspot-Driven Peptide Design via Multi-Fragment Autoregressive Extension

arXiv.org Artificial Intelligence

Peptides, short chains of amino acids, interact with target proteins, making them a unique class of protein-based therapeutics for treating human diseases. Recently, deep generative models have shown great promise in peptide generation. However, several challenges remain in designing effective peptide binders. First, not all residues contribute equally to peptide-target interactions. Second, the generated peptides must adopt valid geometries due to the constraints of peptide bonds. Third, realistic tasks for peptide drug development are still lacking. To address these challenges, we introduce PepHAR, a hot-spot-driven autoregressive generative model for designing peptides targeting specific proteins. Building on the observation that certain hot spot residues have higher interaction potentials, we first use an energy-based density model to fit and sample these key residues. Next, to ensure proper peptide geometry, we autoregressively extend peptide fragments by estimating dihedral angles between residue frames. Finally, we apply an optimization process to iteratively refine fragment assembly, ensuring correct peptide structures. By combining hot spot sampling with fragment-based extension, our approach enables de novo peptide design tailored to a target protein and allows the incorporation of key hot spot residues into peptide scaffolds. Extensive experiments, including peptide design and peptide scaffold generation, demonstrate the strong potential of PepHAR in computational peptide binder design.


Reprogramming Pretrained Target-Specific Diffusion Models for Dual-Target Drug Design

arXiv.org Artificial Intelligence

Dual-target therapeutic strategies have become a compelling approach and attracted significant attention due to various benefits, such as their potential in overcoming drug resistance in cancer therapy. Considering the tremendous success that deep generative models have achieved in structure-based drug design in recent years, we formulate dual-target drug design as a generative task and curate a novel dataset of potential target pairs based on synergistic drug combinations. We propose to design dual-target drugs with diffusion models that are trained on single-target protein-ligand complex pairs. Specifically, we align two pockets in 3D space with protein-ligand binding priors and build two complex graphs with shared ligand nodes for SE(3)-equivariant composed message passing, based on which we derive a composed drift in both 3D and categorical probability space in the generative process. Our algorithm can well transfer the knowledge gained in single-target pretraining to dual-target scenarios in a zero-shot manner. We also repurpose linker design methods as strong baselines for this task. Extensive experiments demonstrate the effectiveness of our method compared with various baselines.


TFG: Unified Training-Free Guidance for Diffusion Models

arXiv.org Artificial Intelligence

Given an unconditional diffusion model and a predictor for a target property of interest (e.g., a classifier), the goal of training-free guidance is to generate samples with desirable target properties without additional training. Existing methods, though effective in various individual applications, often lack theoretical grounding and rigorous testing on extensive benchmarks. As a result, they could even fail on simple tasks, and applying them to a new problem becomes unavoidably difficult. This paper introduces a novel algorithmic framework encompassing existing methods as special cases, unifying the study of training-free guidance into the analysis of an algorithm-agnostic design space. Via theoretical and empirical investigation, we propose an efficient and effective hyper-parameter searching strategy that can be readily applied to any downstream task. We systematically benchmark across 7 diffusion models on 16 tasks with 40 targets, and improve performance by 8.5% on average. Our framework and benchmark offer a solid foundation for conditional generation in a training-free manner.