Surface-based Molecular Design with Multi-modal Flow Matching

Therapeutic peptides show promise in targeting previously undruggable binding sites, with recent advancements in deep generative models enabling full-atom peptide co-design for specific protein receptors. However, the critical role of molecular surfaces in protein-protein interactions (PPIs) has been underexplored. To bridge this gap, we propose an omni-design peptides generation paradigm, called SurfFlow, a novel surface-based generative algorithm that enables comprehensive co-design of sequence, structure, and surface for peptides. SurfFlow employs a multi-modality conditional flow matching (CFM) architecture to learn distributions of surface geometries and biochemical properties, enhancing peptide binding accuracy. Evaluated on the comprehensive PepMerge benchmark, SurfFlow consistently outperforms full-atom baselines across all metrics. These results highlight the advantages of considering molecular surfaces in de novo peptide discovery and demonstrate the potential of integrating multiple protein modalities for more effective therapeutic peptide discovery.

A Semi-supervised Molecular Learning Framework for Activity Cliff Estimation

Machine learning (ML) enables accurate and fast molecular property predictions, which are of interest in drug discovery and material design. Their success is based on the principle of similarity at its heart, assuming that similar molecules exhibit close properties. However, activity cliffs challenge this principle, and their presence leads to a sharp decline in the performance of existing ML algorithms, particularly graph-based methods. To overcome this obstacle under a low-data scenario, we propose a novel semi-supervised learning (SSL) method dubbed SemiMol, which employs predictions on numerous unannotated data as pseudo-signals for subsequent training. Specifically, we introduce an additional instructor model to evaluate the accuracy and trustworthiness of proxy labels because existing pseudo-labeling approaches require probabilistic outputs to reveal the model's confidence and fail to be applied in regression tasks. Moreover, we design a self-adaptive curriculum learning algorithm to progressively move the target model toward hard samples at a controllable pace. Extensive experiments on 30 activity cliff datasets demonstrate that SemiMol significantly enhances graph-based ML architectures and outpasses state-of-the-art pretraining and SSL baselines.

Toward Global Large Language Models in Medicine

Despite continuous advances in medical technology, the global distribution of health care resources remains uneven. The development of large language models (LLMs) has transformed the landscape of medicine and holds promise for improving health care quality and expanding access to medical information globally. However, existing LLMs are primarily trained on high-resource languages, limiting their applicability in global medical scenarios. To address this gap, we constructed GlobMed, a large multilingual medical dataset, containing over 500,000 entries spanning 12 languages, including four low-resource languages. Building on this, we established GlobMed-Bench, which systematically assesses 56 state-of-the-art proprietary and open-weight LLMs across multiple multilingual medical tasks, revealing significant performance disparities across languages, particularly for low-resource languages. Additionally, we introduced GlobMed-LLMs, a suite of multilingual medical LLMs trained on GlobMed, with parameters ranging from 1.7B to 8B. GlobMed-LLMs achieved an average performance improvement of over 40% relative to baseline models, with a more than threefold increase in performance on low-resource languages. Together, these resources provide an important foundation for advancing the equitable development and application of LLMs globally, enabling broader language communities to benefit from technological advances.

From Supervision to Exploration: What Does Protein Language Model Learn During Reinforcement Learning?

Protein language models (PLMs) have advanced computational protein science through large-scale pretraining and scalable architectures. In parallel, reinforcement learning (RL) has broadened exploration and enabled precise multi-objective optimization in protein design. Yet whether RL can push PLMs beyond their pretraining priors to uncover latent sequence-structure-function rules remains unclear. We address this by pairing RL with PLMs across four domains: antimicrobial peptide design, kinase variant optimization, antibody engineering, and inverse folding. Using diverse RL algorithms and model classes, we ask if RL improves sampling efficiency and, more importantly, if it reveals capabilities not captured by supervised learning. Across benchmarks, RL consistently boosts success rates and sample efficiency. Performance follows a three-factor interaction: task headroom, reward fidelity, and policy capacity jointly determine gains. When rewards are accurate and informative, policies have sufficient capacity, and tasks leave room beyond supervised baselines, improvements scale; when rewards are noisy or capacity is constrained, gains saturate despite exploration. This view yields practical guidance for RL in protein design: prioritize reward modeling and calibration before scaling policy size, match algorithm and regularization strength to task difficulty, and allocate capacity where marginal gains are largest. Implementation is available at https://github.com/chq1155/RL-PLM.

Agent KB: Leveraging Cross-Domain Experience for Agentic Problem Solving

As language agents tackle increasingly complex tasks, they struggle with effective error correction and experience reuse across domains. We introduce Agent KB, a hierarchical experience framework that enables complex agentic problem solving via a novel Reason-Retrieve-Refine pipeline. Agent KB addresses a core limitation: agents traditionally cannot learn from each other's experiences. By capturing both high-level strategies and detailed execution logs, Agent KB creates a shared knowledge base that enables cross-agent knowledge transfer. Evaluated on the GAIA benchmark, Agent KB improves success rates by up to 16.28 percentage points. On the most challenging tasks, Claude-3 improves from 38.46% to 57.69%, while GPT-4 improves from 53.49% to 73.26% on intermediate tasks. On SWE-bench code repair, Agent KB enables Claude-3 to improve from 41.33% to 53.33%. Our results suggest that Agent KB provides a modular, framework-agnostic infrastructure for enabling agents to learn from past experiences and generalize successful strategies to new tasks.

Large Language Models are Good Relational Learners

Large language models (LLMs) have demonstrated remarkable capabilities across various domains, yet their application to relational deep learning (RDL) remains underexplored. Existing approaches adapt LLMs by traversing relational links between entities in a database and converting the structured data into flat text documents. Still, this text-based serialization disregards critical relational structures, introduces redundancy, and often exceeds standard LLM context lengths. We introduce Rel-LLM, a novel architecture that utilizes a graph neural network (GNN)- based encoder to generate structured relational prompts for LLMs within a retrieval-augmented generation (RAG) framework. Unlike traditional text-based serialization approaches, our method preserves the inherent relational structure of databases while enabling LLMs to effectively process and reason over complex entity relationships. Specifically, the GNN encoder extracts a local subgraph around an entity to build feature representations that contain relevant entity relationships and temporal dependencies. These representations are transformed into structured prompts using a denormalization process, effectively allowing the LLM to reason over relational structures. Through extensive experiments, we demonstrate that Rel-LLM outperforms existing methods on key RDL tasks, offering a scalable and efficient approach to integrating LLMs with structured data sources. Code is available at https://github.com/smiles724/Rel-LLM.

When to Trust Context: Self-Reflective Debates for Context Reliability

Large language models frequently encounter conflicts between their parametric knowledge and contextual input, often resulting in factual inconsistencies or hallucinations. We propose Self-Reflective Debate for Contextual Reliability (SR-DCR), a lightweight framework that integrates token-level self-confidence with an asymmetric multi-agent debate to adjudicate such conflicts. A critic, deprived of context, challenges a defender who argues from the given passage; a judge model evaluates the debate and determines the context's reliability. The final answer is selected by combining the verdict with model confidence. Experiments on the ClashEval benchmark demonstrate that SR-DCR consistently enhances robustness to misleading context while maintaining accuracy on trustworthy inputs, outperforming both classical debate and confidence-only baselines with minimal computational overhead. The code is available at https://github.com/smiles724/Self-Reflective-Debates.

AnchorAttention: Difference-Aware Sparse Attention with Stripe Granularity

Large Language Models (LLMs) with extended context lengths face significant computational challenges during the pre-filling phase, primarily due to the quadratic complexity of self-attention. Existing methods typically employ dynamic pattern matching and block-sparse low-level implementations. However, their reliance on local information for pattern identification fails to capture global contexts, and the coarse granularity of blocks leads to persistent internal sparsity, resulting in suboptimal accuracy and efficiency. To address these limitations, we propose \textbf{AnchorAttention}, a difference-aware, dynamic sparse attention mechanism that efficiently identifies critical attention regions at a finer stripe granularity while adapting to global contextual information, achieving superior speed and accuracy. AnchorAttention comprises three key components: (1) \textbf{Pattern-based Anchor Computation}, leveraging the commonalities present across all inputs to rapidly compute a set of near-maximum scores as the anchor; (2) \textbf{Difference-aware Stripe Sparsity Identification}, performing difference-aware comparisons with the anchor to quickly obtain discrete coordinates of significant regions in a stripe-like sparsity pattern; (3) \textbf{Fine-grained Sparse Computation}, replacing the traditional contiguous KV block loading approach with simultaneous discrete KV position loading to maximize sparsity rates while preserving full hardware computational potential. With its finer-grained sparsity strategy, \textbf{AnchorAttention} achieves higher sparsity rates at the same recall level, significantly reducing computation time. Compared to previous state-of-the-art methods, at a text length of 128k, it achieves a speedup of 1.44$\times$ while maintaining higher recall rates.

PoseX: AI Defeats Physics Approaches on Protein-Ligand Cross Docking

Recently, significant progress has been made in protein-ligand docking, especially in modern deep learning methods, and some benchmarks were proposed, e.g., PoseBench, Plinder. However, these benchmarks suffer from less practical evaluation setups (e.g., blind docking, self docking), or heavy framework that involves training, raising challenges to assess docking methods efficiently. To fill this gap, we proposed PoseX, an open-source benchmark focusing on self-docking and cross-docking, to evaluate the algorithmic advances practically and comprehensively. Specifically, first, we curate a new evaluation dataset with 718 entries for self docking and 1,312 for cross docking; second, we incorporate 22 docking methods across three methodological categories, including (1) traditional physics-based methods (e.g., Schr\"odinger Glide), (2) AI docking methods (e.g., DiffDock), (3) AI co-folding methods (e.g., AlphaFold3); third, we design a relaxation method as post-processing to minimize conformation energy and refine binding pose; fourth, we released a leaderboard to rank submitted models in real time. We draw some key insights via extensive experiments: (1) AI-based approaches have already surpassed traditional physics-based approaches in overall docking accuracy (RMSD). The longstanding generalization issues that have plagued AI molecular docking have been significantly alleviated in the latest models. (2) The stereochemical deficiencies of AI-based approaches can be greatly alleviated with post-processing relaxation. Combining AI docking methods with the enhanced relaxation method achieves the best performance to date. (3) AI co-folding methods commonly face ligand chirality issues, which cannot be resolved by relaxation. The code, curated dataset and leaderboard are released at https://github.com/CataAI/PoseX.

LocAgent: Graph-Guided LLM Agents for Code Localization

Code localization--identifying precisely where in a codebase changes need to be made--is a fundamental yet challenging task in software maintenance. Existing approaches struggle to efficiently navigate complex codebases when identifying relevant code sections. The challenge lies in bridging natural language problem descriptions with the appropriate code elements, often requiring reasoning across hierarchical structures and multiple dependencies. We introduce LocAgent, a framework that addresses code localization through graph-based representation. By parsing codebases into directed heterogeneous graphs, LocAgent creates a lightweight representation that captures code structures (files, classes, functions) and their dependencies (imports, invocations, inheritance), enabling LLM agents to effectively search and locate relevant entities through powerful multi-hop reasoning. Experimental results on real-world benchmarks demonstrate that our approach significantly enhances accuracy in code localization. Notably, our method with the fine-tuned Qwen-2.5-Coder-Instruct-32B model achieves comparable results to SOTA proprietary models at greatly reduced cost (approximately 86% reduction), reaching up to 92.7% accuracy on file-level localization while improving downstream GitHub issue resolution success rates by 12% for multiple attempts (Pass@10). Our code is available at https://github.com/gersteinlab/LocAgent.