Graph Neural Networks in Modern AI-aided Drug Discovery

Graph neural networks (GNNs), as topology/structure-aware models within deep learning, have emerged as powerful tools for AI-aided drug discovery (AIDD). By directly operating on molecular graphs, GNNs offer an intuitive and expressive framework for learning the complex topological and geometric features of drug-like molecules, cementing their role in modern molecular modeling. This review provides a comprehensive overview of the methodological foundations and representative applications of GNNs in drug discovery, spanning tasks such as molecular property prediction, virtual screening, molecular generation, biomedical knowledge graph construction, and synthesis planning. Particular attention is given to recent methodological advances, including geometric GNNs, interpretable models, uncertainty quantification, scalable graph architectures, and graph generative frameworks. We also discuss how these models integrate with modern deep learning approaches, such as self-supervised learning, multi-task learning, meta-learning and pre-training. Throughout this review, we highlight the practical challenges and methodological bottlenecks encountered when applying GNNs to real-world drug discovery pipelines, and conclude with a discussion on future directions.

You Only Estimate Once: Unified, One-stage, Real-Time Category-level Articulated Object 6D Pose Estimation for Robotic Grasping

This paper addresses the problem of category-level pose estimation for articulated objects in robotic manipulation tasks. Recent works have shown promising results in estimating part pose and size at the category level. However, these approaches primarily follow a complex multi-stage pipeline that first segments part instances in the point cloud and then estimates the Normalized Part Coordinate Space (NPCS) representation for 6D poses. These approaches suffer from high computational costs and low performance in real-time robotic tasks. To address these limitations, we propose YOEO, a single-stage method that simultaneously outputs instance segmentation and NPCS representations in an end-to-end manner. We use a unified network to generate point-wise semantic labels and centroid offsets, allowing points from the same part instance to vote for the same centroid. We further utilize a clustering algorithm to distinguish points based on their estimated centroid distances. Finally, we first separate the NPCS region of each instance. Then, we align the separated regions with the real point cloud to recover the final pose and size. Experimental results on the GAPart dataset demonstrate the pose estimation capabilities of our proposed single-shot method. We also deploy our synthetically-trained model in a real-world setting, providing real-time visual feedback at 200Hz, enabling a physical Kinova robot to interact with unseen articulated objects. This showcases the utility and effectiveness of our proposed method.

Tokenizing Electron Cloud in Protein-Ligand Interaction Learning

The affinity and specificity of protein-molecule binding directly impact functional outcomes, uncovering the mechanisms underlying biological regulation and signal transduction. Most deep-learning-based prediction approaches focus on structures of atoms or fragments. However, quantum chemical properties, such as electronic structures, are the key to unveiling interaction patterns but remain largely underexplored. To bridge this gap, we propose ECBind, a method for tokenizing electron cloud signals into quantized embeddings, enabling their integration into downstream tasks such as binding affinity prediction. By incorporating electron densities, ECBind helps uncover binding modes that cannot be fully represented by atom-level models. Specifically, to remove the redundancy inherent in electron cloud signals, a structure-aware transformer and hierarchical codebooks encode 3D binding sites enriched with electron structures into tokens. These tokenized codes are then used for specific tasks with labels. To extend its applicability to a wider range of scenarios, we utilize knowledge distillation to develop an electron-cloud-agnostic prediction model. Experimentally, ECBind demonstrates state-of-the-art performance across multiple tasks, achieving improvements of 6.42\% and 15.58\% in per-structure Pearson and Spearman correlation coefficients, respectively.

HGCL: Hierarchical Graph Contrastive Learning for User-Item Recommendation

Graph Contrastive Learning (GCL), which fuses graph neural networks with contrastive learning, has evolved as a pivotal tool in user-item recommendations. While promising, existing GCL methods often lack explicit modeling of hierarchical item structures, which represent item similarities across varying resolutions. Such hierarchical item structures are ubiquitous in various items (e.g., online products and local businesses), and reflect their inherent organizational properties that serve as critical signals for enhancing recommendation accuracy. In this paper, we propose Hierarchical Graph Contrastive Learning (HGCL), a novel GCL method that incorporates hierarchical item structures for user-item recommendations. First, HGCL pre-trains a GCL module using cross-layer contrastive learning to obtain user and item representations. Second, HGCL employs a representation compression and clustering method to construct a two-hierarchy user-item bipartite graph. Ultimately, HGCL fine-tunes user and item representations by learning on the hierarchical graph, and then provides recommendations based on user-item interaction scores. Experiments on three widely adopted benchmark datasets ranging from 70K to 382K nodes confirm the superior performance of HGCL over existing baseline models, highlighting the contribution of hierarchical item structures in enhancing GCL methods for recommendation tasks.

CAP-Net: A Unified Network for 6D Pose and Size Estimation of Categorical Articulated Parts from a Single RGB-D Image

This paper tackles category-level pose estimation of articulated objects in robotic manipulation tasks and introduces a new benchmark dataset. While recent methods estimate part poses and sizes at the category level, they often rely on geometric cues and complex multi-stage pipelines that first segment parts from the point cloud, followed by Normalized Part Coordinate Space (NPCS) estimation for 6D poses. These approaches overlook dense semantic cues from RGB images, leading to suboptimal accuracy, particularly for objects with small parts. To address these limitations, we propose a single-stage Network, CAP-Net, for estimating the 6D poses and sizes of Categorical Articulated Parts. This method combines RGB-D features to generate instance segmentation and NPCS representations for each part in an end-to-end manner. CAP-Net uses a unified network to simultaneously predict point-wise class labels, centroid offsets, and NPCS maps. A clustering algorithm then groups points of the same predicted class based on their estimated centroid distances to isolate each part. Finally, the NPCS region of each part is aligned with the point cloud to recover its final pose and size. To bridge the sim-to-real domain gap, we introduce the RGBD-Art dataset, the largest RGB-D articulated dataset to date, featuring photorealistic RGB images and depth noise simulated from real sensors. Experimental evaluations on the RGBD-Art dataset demonstrate that our method significantly outperforms the state-of-the-art approach. Real-world deployments of our model in robotic tasks underscore its robustness and exceptional sim-to-real transfer capabilities, confirming its substantial practical utility. Our dataset, code and pre-trained models are available on the project page.

PolyConf: Unlocking Polymer Conformation Generation through Hierarchical Generative Models

Polymer conformation generation is a critical task that enables atomic-level studies of diverse polymer materials. While significant advances have been made in designing various conformation generation methods for small molecules and proteins, these methods struggle to generate polymer conformations due to polymers' unique structural characteristics. The scarcity of polymer conformation datasets further limits progress, making this promising area largely unexplored. In this work, we propose PolyConf, a pioneering tailored polymer conformation generation method that leverages hierarchical generative models to unlock new possibilities for this task. Specifically, we decompose the polymer conformation into a series of local conformations (i.e., the conformations of its repeating units), generating these local conformations through an autoregressive model. We then generate corresponding orientation transformations via a diffusion model to assemble these local conformations into the complete polymer conformation. Moreover, we develop the first benchmark with a high-quality polymer conformation dataset derived from molecular dynamics simulations to boost related research in this area. The comprehensive evaluation demonstrates that PolyConf consistently generates high-quality polymer conformations, facilitating advancements in polymer modeling and simulation.

A Simple yet Effective DDG Predictor is An Unsupervised Antibody Optimizer and Explainer

The proteins that exist today have been optimized over billions of years of natural evolution, during which nature creates random mutations and selects them. The discovery of functionally promising mutations is challenged by the limited evolutionary accessible regions, i.e., only a small region on the fitness landscape is beneficial. There have been numerous priors used to constrain protein evolution to regions of landscapes with high-fitness variants, among which the change in binding free energy (DDG) of protein complexes upon mutations is one of the most commonly used priors. However, the huge mutation space poses two challenges: (1) how to improve the efficiency of DDG prediction for fast mutation screening; and (2) how to explain mutation preferences and efficiently explore accessible evolutionary regions. To address these challenges, we propose a lightweight DDG predictor (Light-DDG), which adopts a structure-aware Transformer as the backbone and enhances it by knowledge distilled from existing powerful but computationally heavy DDG predictors. Additionally, we augmented, annotated, and released a large-scale dataset containing millions of mutation data for pre-training Light-DDG. We find that such a simple yet effective Light-DDG can serve as a good unsupervised antibody optimizer and explainer. For the target antibody, we propose a novel Mutation Explainer to learn mutation preferences, which accounts for the marginal benefit of each mutation per residue. To further explore accessible evolutionary regions, we conduct preference-guided antibody optimization and evaluate antibody candidates quickly using Light-DDG to identify desirable mutations.

SparseGrasp: Robotic Grasping via 3D Semantic Gaussian Splatting from Sparse Multi-View RGB Images

Language-guided robotic grasping is a rapidly advancing field where robots are instructed using human language to grasp specific objects. However, existing methods often depend on dense camera views and struggle to quickly update scenes, limiting their effectiveness in changeable environments. In contrast, we propose SparseGrasp, a novel open-vocabulary robotic grasping system that operates efficiently with sparse-view RGB images and handles scene updates fastly. Our system builds upon and significantly enhances existing computer vision modules in robotic learning. Specifically, SparseGrasp utilizes DUSt3R to generate a dense point cloud as the initialization for 3D Gaussian Splatting (3DGS), maintaining high fidelity even under sparse supervision. Importantly, SparseGrasp incorporates semantic awareness from recent vision foundation models. To further improve processing efficiency, we repurpose Principal Component Analysis (PCA) to compress features from 2D models. Additionally, we introduce a novel render-and-compare strategy that ensures rapid scene updates, enabling multi-turn grasping in changeable environments. Experimental results show that SparseGrasp significantly outperforms state-of-the-art methods in terms of both speed and adaptability, providing a robust solution for multi-turn grasping in changeable environment.

Learning to Model Graph Structural Information on MLPs via Graph Structure Self-Contrasting

Recent years have witnessed great success in handling graph-related tasks with Graph Neural Networks (GNNs). However, most existing GNNs are based on message passing to perform feature aggregation and transformation, where the structural information is explicitly involved in the forward propagation by coupling with node features through graph convolution at each layer. As a result, subtle feature noise or structure perturbation may cause severe error propagation, resulting in extremely poor robustness. In this paper, we rethink the roles played by graph structural information in graph data training and identify that message passing is not the only path to modeling structural information. Inspired by this, we propose a simple but effective Graph Structure Self-Contrasting (GSSC) framework that learns graph structural information without message passing. The proposed framework is based purely on Multi-Layer Perceptrons (MLPs), where the structural information is only implicitly incorporated as prior knowledge to guide the computation of supervision signals, substituting the explicit message propagation as in GNNs. Specifically, it first applies structural sparsification to remove potentially uninformative or noisy edges in the neighborhood, and then performs structural self-contrasting in the sparsified neighborhood to learn robust node representations. Finally, structural sparsification and self-contrasting are formulated as a bi-level optimization problem and solved in a unified framework. Extensive experiments have qualitatively and quantitatively demonstrated that the GSSC framework can produce truly encouraging performance with better generalization and robustness than other leading competitors.

Polaris: Open-ended Interactive Robotic Manipulation via Syn2Real Visual Grounding and Large Language Models

This paper investigates the task of the open-ended interactive robotic manipulation on table-top scenarios. While recent Large Language Models (LLMs) enhance robots' comprehension of user instructions, their lack of visual grounding constrains their ability to physically interact with the environment. This is because the robot needs to locate the target object for manipulation within the physical workspace. To this end, we introduce an interactive robotic manipulation framework called Polaris, which integrates perception and interaction by utilizing GPT-4 alongside grounded vision models. For precise manipulation, it is essential that such grounded vision models produce detailed object pose for the target object, rather than merely identifying pixels belonging to them in the image. Consequently, we propose a novel Synthetic-to-Real (Syn2Real) pose estimation pipeline. This pipeline utilizes rendered synthetic data for training and is then transferred to real-world manipulation tasks. The real-world performance demonstrates the efficacy of our proposed pipeline and underscores its potential for extension to more general categories. Moreover, real-robot experiments have showcased the impressive performance of our framework in grasping and executing multiple manipulation tasks. This indicates its potential to generalize to scenarios beyond the tabletop. More information and video results are available here: https://star-uu-wang.github.io/Polaris/