arXiv subjects

Zaixi Zhang

Publications and source records attributed to Zaixi Zhang.

At least 19 recordsLinked to original sources

arXiv2026

Agentic-VLA: Efficient Online Adaptation for Vision-Language-Action Models

Vision-Language-Action (VLA) models have emerged as a promising paradigm for robotic manipulation by leveraging pre-trained vision-language representations. However, current VLA training methods suffer from two critical limitations: poor generalization to novel environments and low training efficiency requiring extensive demonstrations. We introduce Agentic-VLA, an agentic training framework that enables VLAs to efficiently adapt online through three key innovations: (1) Adaptive Reward Synthesis, which dynamically generates and adjusts reward functions based on the VLA's current capabilities and task complexity, decomposing complex tasks into learnable sub-goals for curriculum learning; (2) Language-Guided Exploration, where a critic model provides structured guidance for systematic exploration rather than random sampling; and (3) Experience Memory,which stores and retrieves task-relevant policy weights for warm-starting adaptation to similar tasks. We evaluate Agentic-VLA on the LIBERO benchmark, achieving substantial improvements: +12.3% on long-horizon tasks, +28.5% in 1-shot learning, and enabling cross-task transfer from 0% to 31.2% without task-specific demonstrations. Our framework also demonstrates 2.4x faster convergence compared to existing online adaptation methods. Beyond LIBERO, Agentic-VLA retains its advantage on the dual-arm RoboTwin 2.0 benchmark, including under its randomized Hard setting. These results establish Agentic-VLA as a significant step toward truly adaptive VLA systems capable of continuous learning in deployment.

cs.RO↗

arXiv2026

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

Existing protein-ligand docking studies typically focus on the self-docking scenario, which is less practical in real applications. Moreover, some studies involve heavy frameworks requiring extensive training, posing challenges for convenient and efficient assessment of docking methods. To fill these gaps, we design PoseX, an open-source benchmark to evaluate both self-docking and cross-docking, enabling a practical and comprehensive assessment of algorithmic advances. Specifically, we curated a novel dataset comprising 718 entries for self-docking and 1,312 entries for cross-docking; second, we incorporated 23 docking methods in three methodological categories, including physics-based methods (e.g., Schrödinger Glide), AI docking methods (e.g., DiffDock) and AI co-folding methods (e.g., AlphaFold3); third, we developed a relaxation method for post-processing to minimize conformational energy and refine binding poses; fourth, we built a leaderboard to rank submitted models in real-time. We derived some key insights and conclusions from extensive experiments: (1) AI approaches have consistently outperformed physics-based methods in overall docking success rate. (2) Most intra- and intermolecular clashes of AI approaches can be greatly alleviated with relaxation, which means combining AI modeling with physics-based post-processing could achieve excellent performance. (3) AI co-folding methods exhibit ligand chirality issues, except for Boltz-1x, which introduced physics-inspired potentials to fix hallucinations, suggesting modeling on stereochemistry improves the structural plausibility markedly. (4) Specifying binding pockets significantly promotes docking performance, indicating that pocket information can be leveraged adequately, particularly for AI co-folding methods, in future modeling efforts. The code, dataset, and leaderboard are released at https://github.com/CataAI/PoseX.

cs.LG↗

arXiv2026

BioMiner: A Multi-modal System for Automated Mining of Protein-Ligand Bioactivity Data from Literature

Protein-ligand bioactivity data published in the literature are essential for drug discovery, yet manual curation struggles to keep pace with rapidly growing literature. Automated bioactivity extraction remains challenging because it requires not only interpreting biochemical semantics distributed across text, tables, and figures, but also reconstructing chemically exact ligand structures (e.g., Markush structures). To address this bottleneck, we introduce BioMiner, a multi-modal extraction framework that explicitly separates bioactivity semantic interpretation from ligand structure construction. Within BioMiner, bioactivity semantics are inferred through direct reasoning, while chemical structures are resolved via a chemical-structure-grounded visual semantic reasoning paradigm, in which multi-modal large language models operate on chemically grounded visual representations to infer inter-structure relationships, and exact molecular construction is delegated to domain chemistry tools. For rigorous evaluation and method development, we further establish BioVista, a comprehensive benchmark comprising 16,457 bioactivity entries curated from 500 publications. BioMiner validates its extraction ability and provides a quantitative baseline, achieving an F1 score of 0.32 for bioactivity triplets. BioMiner's practical utility is demonstrated via three applications: (1) extracting 82,262 data from 11,683 papers to build a pre-training database that improves downstream models performance by 3.9%; (2) enabling a human-in-the-loop workflow that doubles the number of high-quality NLRP3 bioactivity data, helping 38.6% improvement over 28 QSAR models and identification of 16 hit candidates with novel scaffolds; and (3) accelerating protein-ligand complex bioactivity annotation, achieving a 5.59-fold speed increase and 5.75% accuracy improvement over manual workflows in PoseBusters dataset.

cs.AI↗

arXiv2026

Beyond Affinity: A Benchmark of 1D, 2D, and 3D Methods Reveals Critical Trade-offs in Structure-Based Drug Design

Currently, the field of structure-based drug design is dominated by three main types of algorithms: search-based algorithms, deep generative models, and reinforcement learning. While existing works have typically focused on comparing models within a single algorithmic category, cross-algorithm comparisons remain scarce. In this paper, to fill the gap, we establish a benchmark to evaluate the performance of fifteen models across these different algorithmic foundations by assessing the pharmaceutical properties of the generated molecules and their docking affinities and poses with specified target proteins. We highlight the unique advantages of each algorithmic approach and offer recommendations for the design of future SBDD models. We emphasize that 1D/2D ligand-centric drug design methods can be used in SBDD by treating the docking function as a black-box oracle, which is typically neglected. Our evaluation reveals distinct patterns across model categories. 3D structure-based models excel in binding affinities but show inconsistencies in chemical validity and pose quality. 1D models demonstrate reliable performance in standard molecular metrics but rarely achieve optimal binding affinities. 2D models offer balanced performance, maintaining high chemical validity while achieving moderate binding scores. Through detailed analysis across multiple protein targets, we identify key improvement areas for each model category, providing insights for researchers to combine strengths of different approaches while addressing their limitations. All the code that are used for benchmarking is available in https://github.com/zkysfls/2025-sbdd-benchmark

cs.LG↗

arXiv2025

LabOS: The AI-XR Co-Scientist That Sees and Works With Humans

Modern science advances fastest when thought meets action. LabOS represents the first AI co-scientist that unites computational reasoning with physical experimentation through multimodal perception, self-evolving agents, and Extended-Reality(XR)-enabled human-AI collaboration. By connecting multi-model AI agents, smart glasses, and robots, LabOS allows AI to see what scientists see, understand experimental context, and assist in real-time execution. Across applications -- from cancer immunotherapy target discovery to stem-cell engineering and material science -- LabOS shows that AI can move beyond computational design to participation, turning the laboratory into an intelligent, collaborative environment where human and machine discovery evolve together.

cs.AI↗

arXiv2025

Evolution without an Oracle: Driving Effective Evolution with LLM Judges

The integration of Large Language Models (LLMs) with Evolutionary Computation (EC) has unlocked new frontiers in scientific discovery but remains shackled by a fundamental constraint: the reliance on an Oracle--an objective, machine-computable fitness function. This paper breaks this barrier by asking: Can evolution thrive in a purely subjective landscape governed solely by LLM judges? We introduce MADE (Multi-Agent Decomposed Evolution), a framework that tames the inherent noise of subjective evaluation through "Problem Specification." By decomposing vague instructions into specific, verifiable sub-requirements, MADE transforms high-variance LLM feedback into stable, precise selection pressure. The results are transformative: across complex benchmarks like DevAI and InfoBench, MADE outperforms strong baselines by over 50% in software requirement satisfaction (39.9% to 61.9%) and achieves a 95% perfect pass rate on complex instruction following. This work validates a fundamental paradigm shift: moving from optimizing "computable metrics" to "describable qualities," thereby unlocking evolutionary optimization for the vast open-ended domains where no ground truth exists.

cs.SE↗

arXiv2025

Generative AI for Biosciences: Emerging Threats and Roadmap to Biosecurity

The rapid adoption of generative artificial intelligence (GenAI) in the biosciences is transforming biotechnology, medicine, and synthetic biology. Yet this advancement is intrinsically linked to new vulnerabilities, as GenAI lowers the barrier to misuse and introduces novel biosecurity threats, such as generating synthetic viral proteins or toxins. These dual-use risks are often overlooked, as existing safety guardrails remain fragile and can be circumvented through deceptive prompts or jailbreak techniques. In this Perspective, we first outline the current state of GenAI in the biosciences and emerging threat vectors ranging from jailbreak attacks and privacy risks to the dual-use challenges posed by autonomous AI agents. We then examine urgent gaps in regulation and oversight, drawing on insights from 130 expert interviews across academia, government, industry, and policy. A large majority ($\approx 76$\%) expressed concern over AI misuse in biology, and 74\% called for the development of new governance frameworks. Finally, we explore technical pathways to mitigation, advocating a multi-layered approach to GenAI safety. These defenses include rigorous data filtering, alignment with ethical principles during development, and real-time monitoring to block harmful requests. Together, these strategies provide a blueprint for embedding security throughout the GenAI lifecycle. As GenAI becomes integrated into the biosciences, safeguarding this frontier requires an immediate commitment to both adaptive governance and secure-by-design technologies.

cs.CR↗

arXiv2025

SafeProtein: Red-Teaming Framework and Benchmark for Protein Foundation Models

Proteins play crucial roles in almost all biological processes. The advancement of deep learning has greatly accelerated the development of protein foundation models, leading to significant successes in protein understanding and design. However, the lack of systematic red-teaming for these models has raised serious concerns about their potential misuse, such as generating proteins with biological safety risks. This paper introduces SafeProtein, the first red-teaming framework designed for protein foundation models to the best of our knowledge. SafeProtein combines multimodal prompt engineering and heuristic beam search to systematically design red-teaming methods and conduct tests on protein foundation models. We also curated SafeProtein-Bench, which includes a manually constructed red-teaming benchmark dataset and a comprehensive evaluation protocol. SafeProtein achieved continuous jailbreaks on state-of-the-art protein foundation models (up to 70% attack success rate for ESM3), revealing potential biological safety risks in current protein foundation models and providing insights for the development of robust security protection technologies for frontier models. The codes will be made publicly available at https://github.com/jigang-fan/SafeProtein.

cs.LG↗

arXiv2025

Securing the Language of Life: Inheritable Watermarks from DNA Language Models to Proteins

DNA language models have revolutionized our ability to understand and design DNA sequences--the fundamental language of life--with unprecedented precision, enabling transformative applications in therapeutics, synthetic biology, and gene editing. However, this capability also poses substantial dual-use risks, including the potential for creating pathogens, viruses, and even bioweapons. To address these biosecurity challenges, we introduce two innovative watermarking techniques to reliably track the designed DNA: DNAMark and CentralMark. DNAMark employs synonymous codon substitutions to embed watermarks in DNA sequences while preserving the original function. CentralMark further advances this by creating inheritable watermarks that transfer from DNA to translated proteins, leveraging protein embeddings to ensure detection across the central dogma. Both methods utilize semantic embeddings to generate watermark logits, enhancing robustness against natural mutations, synthesis errors, and adversarial attacks. Evaluated on our therapeutic DNA benchmark, DNAMark and CentralMark achieve F1 detection scores above 0.85 under various conditions, while maintaining over 60% sequence similarity to ground truth and degeneracy scores below 15%. A case study on the CRISPR-Cas9 system underscores CentralMark's utility in real-world settings. This work establishes a vital framework for securing DNA language models, balancing innovation with accountability to mitigate biosecurity risks.

q-bio.GN↗

arXiv2025

A Biosecurity Agent for Lifecycle LLM Biosecurity Alignment

Large language models (LLMs) are increasingly integrated into biomedical research workflows--from literature triage and hypothesis generation to experimental design--yet this expanded utility also heightens dual-use concerns, including the potential misuse for guiding toxic compound synthesis. In response, this study shows a Biosecurity Agent that comprises four coordinated modes across the model lifecycle: dataset sanitization, preference alignment, run-time guardrails, and automated red teaming. For dataset sanitization (Mode 1), evaluation is conducted on CORD-19, a COVID-19 Open Research Dataset of coronavirus-related scholarly articles. We define three sanitization tiers--L1 (compact, high-precision), L2 (human-curated biosafety terms), and L3 (comprehensive union)--with removal rates rising from 0.46% to 70.40%, illustrating the safety-utility trade-off. For preference alignment (Mode 2), DPO with LoRA adapters internalizes refusals and safe completions, reducing end-to-end attack success rate (ASR) from 59.7% to 3.0%. At inference (Mode 3), run-time guardrails across L1-L3 show the expected security-usability trade-off: L2 achieves the best balance (F1 = 0.720, precision = 0.900, recall = 0.600, FPR =0.067), while L3 offers stronger jailbreak resistance at the cost of higher false positives. Under continuous automated red-teaming (Mode 4), no successful jailbreaks are observed under the tested protocol. Taken together, our biosecurity agent offers an auditable, lifecycle-aligned framework that reduces attack success while preserving benign utility, providing safeguards for the use of LLMs in scientific research and setting a precedent for future agent-level security protections.

cs.CR↗

arXiv2025

STELLA: Self-Evolving LLM Agent for Biomedical Research

The rapid growth of biomedical data, tools, and literature has created a fragmented research landscape that outpaces human expertise. While AI agents offer a solution, they typically rely on static, manually curated toolsets, limiting their ability to adapt and scale. Here, we introduce STELLA, a self-evolving AI agent designed to overcome these limitations. STELLA employs a multi-agent architecture that autonomously improves its own capabilities through two core mechanisms: an evolving Template Library for reasoning strategies and a dynamic Tool Ocean that expands as a Tool Creation Agent automatically discovers and integrates new bioinformatics tools. This allows STELLA to learn from experience. We demonstrate that STELLA achieves state-of-the-art accuracy on a suite of biomedical benchmarks, scoring approximately 26\% on Humanity's Last Exam: Biomedicine, 54\% on LAB-Bench: DBQA, and 63\% on LAB-Bench: LitQA, outperforming leading models by up to 6 percentage points. More importantly, we show that its performance systematically improves with experience; for instance, its accuracy on the Humanity's Last Exam benchmark almost doubles with increased trials. STELLA represents a significant advance towards AI Agent systems that can learn and grow, dynamically scaling their expertise to accelerate the pace of biomedical discovery.

cs.AI↗

arXiv2025

GeneBreaker: Jailbreak Attacks against DNA Language Models with Pathogenicity Guidance

DNA, encoding genetic instructions for almost all living organisms, fuels groundbreaking advances in genomics and synthetic biology. Recently, DNA Foundation Models have achieved success in designing synthetic functional DNA sequences, even whole genomes, but their susceptibility to jailbreaking remains underexplored, leading to potential concern of generating harmful sequences such as pathogens or toxin-producing genes. In this paper, we introduce GeneBreaker, the first framework to systematically evaluate jailbreak vulnerabilities of DNA foundation models. GeneBreaker employs (1) an LLM agent with customized bioinformatic tools to design high-homology, non-pathogenic jailbreaking prompts, (2) beam search guided by PathoLM and log-probability heuristics to steer generation toward pathogen-like sequences, and (3) a BLAST-based evaluation pipeline against a curated Human Pathogen Database (JailbreakDNABench) to detect successful jailbreaks. Evaluated on our JailbreakDNABench, GeneBreaker successfully jailbreaks the latest Evo series models across 6 viral categories consistently (up to 60\% Attack Success Rate for Evo2-40B). Further case studies on SARS-CoV-2 spike protein and HIV-1 envelope protein demonstrate the sequence and structural fidelity of jailbreak output, while evolutionary modeling of SARS-CoV-2 underscores biosecurity risks. Our findings also reveal that scaling DNA foundation models amplifies dual-use risks, motivating enhanced safety alignment and tracing mechanisms. Our code is at https://github.com/zaixizhang/GeneBreaker.

cs.CR↗

arXiv2025

GraphPrompter: Multi-stage Adaptive Prompt Optimization for Graph In-Context Learning

Graph In-Context Learning, with the ability to adapt pre-trained graph models to novel and diverse downstream graphs without updating any parameters, has gained much attention in the community. The key to graph in-context learning is to perform downstream graphs conditioned on chosen prompt examples. Existing methods randomly select subgraphs or edges as prompts, leading to noisy graph prompts and inferior model performance. Additionally, due to the gap between pre-training and testing graphs, when the number of classes in the testing graphs is much greater than that in the training, the in-context learning ability will also significantly deteriorate. To tackle the aforementioned challenges, we develop a multi-stage adaptive prompt optimization method GraphPrompter, which optimizes the entire process of generating, selecting, and using graph prompts for better in-context learning capabilities. Firstly, Prompt Generator introduces a reconstruction layer to highlight the most informative edges and reduce irrelevant noise for graph prompt construction. Furthermore, in the selection stage, Prompt Selector employs the $k$-nearest neighbors algorithm and pre-trained selection layers to dynamically choose appropriate samples and minimize the influence of irrelevant prompts. Finally, we leverage a Prompt Augmenter with a cache replacement strategy to enhance the generalization capability of the pre-trained model on new datasets. Extensive experiments show that GraphPrompter effectively enhances the in-context learning ability of graph models. On average across all the settings, our approach surpasses the state-of-the-art baselines by over 8%. Our code is released at https://github.com/karin0018/GraphPrompter.

cs.LG↗

arXiv2025

From Understanding to Excelling: Template-Free Algorithm Design through Structural-Functional Co-Evolution

Large language models (LLMs) have greatly accelerated the automation of algorithm generation and optimization. However, current methods such as EoH and FunSearch mainly rely on predefined templates and expert-specified functions that focus solely on the local evolution of key functionalities. Consequently, they fail to fully leverage the synergistic benefits of the overall architecture and the potential of global optimization. In this paper, we introduce an end-to-end algorithm generation and optimization framework based on LLMs. Our approach utilizes the deep semantic understanding of LLMs to convert natural language requirements or human-authored papers into code solutions, and employs a two-dimensional co-evolution strategy to optimize both functional and structural aspects. This closed-loop process spans problem analysis, code generation, and global optimization, automatically identifying key algorithm modules for multi-level joint optimization and continually enhancing performance and design innovation. Extensive experiments demonstrate that our method outperforms traditional local optimization approaches in both performance and innovation, while also exhibiting strong adaptability to unknown environments and breakthrough potential in structural design. By building on human research, our framework generates and optimizes novel algorithms that surpass those designed by human experts, broadening the applicability of LLMs for algorithm design and providing a novel solution pathway for automated algorithm development.

cs.SE↗

arXiv2024

Model Inversion Attacks Through Target-Specific Conditional Diffusion Models

Model inversion attacks (MIAs) aim to reconstruct private images from a target classifier's training set, thereby raising privacy concerns in AI applications. Previous GAN-based MIAs tend to suffer from inferior generative fidelity due to GAN's inherent flaws and biased optimization within latent space. To alleviate these issues, leveraging on diffusion models' remarkable synthesis capabilities, we propose Diffusion-based Model Inversion (Diff-MI) attacks. Specifically, we introduce a novel target-specific conditional diffusion model (CDM) to purposely approximate target classifier's private distribution and achieve superior accuracy-fidelity balance. Our method involves a two-step learning paradigm. Step-1 incorporates the target classifier into the entire CDM learning under a pretrain-then-finetune fashion, with creating pseudo-labels as model conditions in pretraining and adjusting specified layers with image predictions in fine-tuning. Step-2 presents an iterative image reconstruction method, further enhancing the attack performance through a combination of diffusion priors and target knowledge. Additionally, we propose an improved max-margin loss that replaces the hard max with top-k maxes, fully leveraging feature information and soft labels from the target classifier. Extensive experiments demonstrate that Diff-MI significantly improves generative fidelity with an average decrease of 20\% in FID while maintaining competitive attack accuracy compared to state-of-the-art methods across various datasets and models. Our code is available at: \url{https://github.com/Ouxiang-Li/Diff-MI}.

cs.CV↗

arXiv2024

Geometric Deep Learning for Structure-Based Drug Design: A Survey

Structure-based drug design (SBDD) leverages the three-dimensional geometry of proteins to identify potential drug candidates. Traditional approaches, rooted in physicochemical modeling and domain expertise, are often resource-intensive. Recent advancements in geometric deep learning, which effectively integrate and process 3D geometric data, alongside breakthroughs in accurate protein structure predictions from tools like AlphaFold, have significantly propelled the field forward. This paper systematically reviews the state-of-the-art in geometric deep learning for SBDD. We begin by outlining foundational tasks in SBDD, discussing prevalent 3D protein representations, and highlighting representative predictive and generative models. Next, we provide an in-depth review of key tasks, including binding site prediction, binding pose generation, de novo molecule generation, linker design, protein pocket generation, and binding affinity prediction. For each task, we present formal problem definitions, key methods, datasets, evaluation metrics, and performance benchmarks. Lastly, we explore current challenges and future opportunities in SBDD. Challenges include oversimplified problem formulations, limited out-of-distribution generalization, biosecurity concerns related to the misuse of structural data, insufficient evaluation metrics and large-scale benchmarks, and the need for experimental validation and enhanced model interpretability. Opportunities lie in leveraging multimodal datasets, integrating domain knowledge, developing comprehensive benchmarks, establishing criteria aligned with clinical outcomes, and designing foundation models to expand the scope of design tasks. We also curate \url{https://github.com/zaixizhang/Awesome-SBDD}, reflecting ongoing contributions and new datasets in SBDD.

q-bio.QM↗

arXiv2024

FoldMark: Protecting Protein Generative Models with Watermarking

Protein structure is key to understanding protein function and is essential for progress in bioengineering, drug discovery, and molecular biology. Recently, with the incorporation of generative AI, the power and accuracy of computational protein structure prediction/design have been improved significantly. However, ethical concerns such as copyright protection and harmful content generation (biosecurity) pose challenges to the wide implementation of protein generative models. Here, we investigate whether it is possible to embed watermarks into protein generative models and their outputs for copyright authentication and the tracking of generated structures. As a proof of concept, we propose a two-stage method FoldMark as a generalized watermarking strategy for protein generative models. FoldMark first pretrain watermark encoder and decoder, which can minorly adjust protein structures to embed user-specific information and faithfully recover the information from the encoded structure. In the second step, protein generative models are fine-tuned with watermark-conditioned Low-Rank Adaptation (LoRA) modules to preserve generation quality while learning to generate watermarked structures with high recovery rates. Extensive experiments are conducted on open-source protein structure prediction models (e.g., ESMFold and MultiFlow) and de novo structure design models (e.g., FrameDiff and FoldFlow) and we demonstrate that our method is effective across all these generative models. Meanwhile, our watermarking framework only exerts a negligible impact on the original protein structure quality and is robust under potential post-processing and adaptive attacks.

cs.CR↗

arXiv2024

DeltaDock: A Unified Framework for Accurate, Efficient, and Physically Reliable Molecular Docking

Molecular docking, a technique for predicting ligand binding poses, is crucial in structure-based drug design for understanding protein-ligand interactions. Recent advancements in docking methods, particularly those leveraging geometric deep learning (GDL), have demonstrated significant efficiency and accuracy advantages over traditional sampling methods. Despite these advancements, current methods are often tailored for specific docking settings, and limitations such as the neglect of protein side-chain structures, difficulties in handling large binding pockets, and challenges in predicting physically valid structures exist. To accommodate various docking settings and achieve accurate, efficient, and physically reliable docking, we propose a novel two-stage docking framework, DeltaDock, consisting of pocket prediction and site-specific docking. We innovatively reframe the pocket prediction task as a pocket-ligand alignment problem rather than direct prediction in the first stage. Then we follow a bi-level coarse-to-fine iterative refinement process to perform site-specific docking. Comprehensive experiments demonstrate the superior performance of DeltaDock. Notably, in the blind docking setting, DeltaDock achieves a 31\% relative improvement over the docking success rate compared with the previous state-of-the-art GDL model. With the consideration of physical validity, this improvement increases to about 300\%.

q-bio.BM↗