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Xuan Lin

Publications and source records attributed to Xuan Lin.

At least 19 recordsLinked to original sources
arXiv2026

A Systematic Evaluation of Molecule Generation Models for De Novo Drug Design: From Benchmarks to Practical Insights

Molecule generation has emerged as a powerful computational tool for de novo drug design, enabling the exploration of chemical space beyond the limits of conventional virtual screening. The field has progressed rapidly, driven by advances in molecular representations, generative architectures, and target-aware modeling strategies. However, existing reviews typically address specific model families or application scenarios in isolation, rather than offering an integrated perspective on how these components collectively form a coherent generation workflow. In this review, we present a comprehensive evaluation of molecule generation models for de novo drug design, covering 82 methods across five deep generative frameworks, including recurrent neural network (RNN)- and Transformer-based models, variational autoencoders (VAEs), generative adversarial networks (GANs), flow-based models, and diffusion models. We first summarize widely used benchmarks and molecular representations, and then examine the methodological principles underlying both general and pocket-conditioned generation. A central contribution of this work is a systematic synthesis and comparative analysis of reported performance across commonly used benchmarks and evaluation metrics. We also summarize representative experimentally validated case studies. Looking ahead, we discuss future directions in standardized 3D data, interaction-aware generation, receptor flexibility, and multi-objective molecular design, with the aim of improving the reliability and experimental relevance of molecule generation. All collected benchmark resources, evaluation metrics, and model references are provided in a publicly accessible repository at https://github.com/JacklinGroup/molecule-generation-review.

cs.LG↗
arXiv2026

Learning Molecular Representations from Cellular Phenotypes with Structure Preservation

Phenotypic drug discovery enables the discovery of functional relationships between molecular structures and cellular responses. However, existing multimodal representation learning methods often optimize cross-modal alignment without considering the intrinsic organization of chemical space, resulting in distorted molecular representations and loss of structural information. We propose \textbf{PhenMol}, a structure-preserving framework for phenotype-aware molecular representation learning. PhenMol disentangles molecular and cellular representations into shared and private components, enabling phenotype-guided alignment while preserving chemical structures through a dedicated molecular branch. This design integrates cellular phenotype information without disrupting molecular neighborhood organization. Experiments on approximately $3.04 \times 10^{4}$ molecule--cell morphology pairs demonstrate that PhenMol improves molecular property prediction across 270 bioactivity tasks, molecule--phenotype retrieval, and clinical trial outcome prediction. Moreover, ECFP4-based structural analysis shows that PhenMol better preserves molecular neighborhoods and reduces embedding distortion compared with existing multimodal alignment methods. These results highlight the importance of structure-aware constraints in multimodal molecular representation learning and provide an effective approach for integrating cellular phenotypes with chemical knowledge for drug discovery.

cs.LG↗
arXiv2026

CryoProt: A Protein Pretraining Framework with Cross-Box Interactions on Cryo-EM Density Maps

Despite the growing availability of cryo-electron microscopy (cryo-EM) density maps, effectively leveraging them for protein representation remains challenging. First, current methods lack a general-purpose protein pretraining framework tailored for cryo-EM density maps, designed for protein-related property prediction. Second, existing approaches typically partition density maps into local box regions and model them independently, overlooking interactions across boxes which are essential for capturing global structural context in cryo-EM density map. To address these challenges, we propose CryoProt, a protein pretraining framework designed for cryo-EM density maps. CryoProt introduces a Map Encoder based on multi-head latent attention (MLA), where box-level representations interact through a shared latent space, enabling explicit modeling of cross-box dependencies within the density map. Furthermore, we adopt a multi-task pretraining strategy to learn generalizable representations that can be effectively transferred to diverse downstream tasks, such as protein flexibility prediction, where cryo-EM density maps are not required and can be inferred implicitly by the pretrained model. Experimental results demonstrate that CryoProt consistently outperforms existing state-of-the-art methods across multiple benchmarks, achieving up to 12% improvement over the best-performing baselines, highlighting the importance of modeling cross-box interactions in cryo-EM data. The source code is publicly available at https://anonymous.4open.science/r/CryoProt.

cs.LG↗
arXiv2026

A Triple-Modal Contrastive Learning Framework with Sequence, Graph, and 3D Features for Drug-Target Interaction Prediction

Accurate prediction of drug-target interactions (DTI) is critical for drug discovery. Existing methods often rely on single-modal representations (e.g., sequences or graphs) or combine only two modalities, overlooking 3D structural features. To address this challenge, we propose TriMod-DTI, a triple-modal contrastive learning framework that incorporates 1D sequences, 2D graphs, and 3D structures of drugs and proteins, obtaining the universal and complementary feature representations for DTI prediction. We design a Feature Extractor to capture drug and target features across the three modalities, thereby enriching their representations. We further propose a triple-modal contrastive learning strategy to align different modal representations of the same drug or protein in the latent space. By constructing cross-modal positive and negative sample pairs, this approach enhances the model's discriminative ability. Experiments on three benchmark datasets demonstrate that TriMod-DTI outperforms state-of-the-art methods. The ablation studies validate the contributions of each modality. Moreover, case studies highlight its practical potential for DTI prediction and drug discovery.

cs.LG↗
arXiv2026

Deep-layer limit and stability analysis of the basic forward-backward-splitting induced network (II): learning problems

Deep unfolding neural networks derived from iterative optimization schemes and numerical ordinary/partial differential equations (ODEs/PDEs) have attracted much attention in data science over the last decade. Therein, numerous important network architectures were constructed from the basic forward-backward-splitting (FBS) algorithm. In this paper, we continue our research on the most basic FBS-induced network, an architecture unrolled from the original FBS algorithm by incorporating direct parameter relaxations. Following the difference/differential inclusion formulations in our previous forward system analyses, we here consider some theoretical aspects of corresponding learning problems. Under some mild assumptions, we establish a general convergence property of the training problem of the basic FBS-induced network to the learning problem of the deep-layer limit system, implying a $\Gamma$-convergence argument showing that any cluster point of the optimal learning parameters for the network is a solution to the learning problem of the deep-layer limit system. A qualitative analysis of perturbation stabilities of these learning problems is also presented. A simple numerical experiment is conducted to validate our main general convergence result.

cs.LG↗
arXiv2026

RubricEval: A Rubric-Level Meta-Evaluation Benchmark for LLM Judges in Instruction Following

Rubric-based evaluation has become a prevailing paradigm for evaluating instruction following in large language models (LLMs). Despite its widespread use, the reliability of these rubric-level evaluations remains unclear, calling for meta-evaluation. However, prior meta-evaluation efforts largely focus on the response level, failing to assess the fine-grained judgment accuracy that rubric-based evaluation relies on. To bridge this gap, we introduce RubricEval. Our benchmark features: (1) the first rubric-level meta-evaluation benchmark for instruction following, (2) diverse instructions and responses spanning multiple categories and model sources, and (3) a substantial set of 3,486 quality-controlled instances, along with Easy/Hard subsets that better differentiates judge performance. Our experiments reveal that rubric-level judging remains far from solved: even GPT-4o, a widely adopted judge in instruction-following benchmarks, achieves only 55.97% on Hard subset. Considering evaluation paradigm, rubric-level evaluation outperforms checklist-level, explicit reasoning improves accuracy, and both together reduce inter-judge variance. Through our established rubric taxonomy, we further identify common failure modes and offer actionable insights for reliable instruction-following evaluation.

cs.AI↗
arXiv2026

An Industrial-Scale Insurance LLM Achieving Verifiable Domain Mastery and Hallucination Control without Competence Trade-offs

Adapting Large Language Models (LLMs) to high-stakes vertical domains like insurance presents a significant challenge: scenarios demand strict adherence to complex regulations and business logic with zero tolerance for hallucinations. Existing approaches often suffer from a Competency Trade-off - sacrificing general intelligence for domain expertise - or rely heavily on RAG without intrinsic reasoning. To bridge this gap, we present INS-S1, an insurance-specific LLM family trained via a novel end-to-end alignment paradigm. Our approach features two methodological innovations: (1) A Verifiable Data Synthesis System that constructs hierarchical datasets for actuarial reasoning and compliance; and (2) A Progressive SFT-RL Curriculum Framework that integrates dynamic data annealing with a synergistic mix of Verified Reasoning (RLVR) and AI Feedback (RLAIF). By optimizing data ratios and reward signals, this framework enforces domain constraints while preventing catastrophic forgetting. Additionally, we release INSEva, the most comprehensive insurance benchmark to date (39k+ samples). Extensive experiments show that INS-S1 achieves SOTA performance on domain tasks, significantly outperforming DeepSeek-R1 and Gemini-2.5-Pro. Crucially, it maintains top-tier general capabilities and achieves a record-low 0.6% hallucination rate (HHEM). Our results demonstrate that rigorous domain specialization can be achieved without compromising general intelligence.

cs.CL↗
arXiv2026

Softmax Linear Attention: Reclaiming Global Competition

While linear attention reduces the quadratic complexity of standard Transformers to linear time, it often lags behind in expressivity due to the removal of softmax normalization. This omission eliminates \emph{global competition}, a critical mechanism that enables models to sharply focus on relevant information amidst long-context noise. In this work, we propose \textbf{Softmax Linear Attention (SLA)}, a framework designed to restore this competitive selection without sacrificing efficiency. By lifting the softmax operation from the token level to the head level, SLA leverages attention heads as coarse semantic slots, applying a competitive gating mechanism to dynamically select the most relevant subspaces. This reintroduces the ``winner-take-all'' dynamics essential for precise retrieval and robust long-context understanding. Distinct from prior methods that focus on refining local kernel functions, SLA adopts a broader perspective by exploiting the higher-level multi-head aggregation structure. Extensive experiments demonstrate that SLA consistently enhances state-of-the-art linear baselines (RetNet, GLA, GDN) across language modeling and long-context benchmarks, particularly in challenging retrieval scenarios where it significantly boosts robustness against noise, validating its capability to restore precise focus while maintaining linear complexity.

cs.LG↗
arXiv2025

MolBridge: Atom-Level Joint Graph Refinement for Robust Drug-Drug Interaction Event Prediction

Drug combinations offer therapeutic benefits but also carry the risk of adverse drug-drug interactions (DDIs), especially under complex molecular structures. Accurate DDI event prediction requires capturing fine-grained inter-drug relationships, which are critical for modeling metabolic mechanisms such as enzyme-mediated competition. However, existing approaches typically rely on isolated drug representations and fail to explicitly model atom-level cross-molecular interactions, limiting their effectiveness across diverse molecular complexities and DDI type distributions. To address these limitations, we propose MolBridge, a novel atom-level joint graph refinement framework for robust DDI event prediction. MolBridge constructs a joint graph that integrates atomic structures of drug pairs, enabling direct modeling of inter-drug associations. A central challenge in such joint graph settings is the potential loss of information caused by over-smoothing when modeling long-range atomic dependencies. To overcome this, we introduce a structure consistency module that iteratively refines node features while preserving the global structural context. This joint design allows MolBridge to effectively learn both local and global interaction outperforms state-of-the-art baselines, achieving superior performance across long-tail and inductive scenarios. patterns, yielding robust representations across both frequent and rare DDI types. Extensive experiments on two benchmark datasets show that MolBridge consistently. These results demonstrate the advantages of fine-grained graph refinement in improving the accuracy, robustness, and mechanistic interpretability of DDI event prediction.This work contributes to Web Mining and Content Analysis by developing graph-based methods for mining and analyzing drug-drug interaction networks.

cs.LG↗
arXiv2025

Towards Tighter Convex Relaxation of Mixed-Integer Programs: Leveraging Logic Network Flow for Task and Motion Planning

This paper proposes an optimization-based task and motion planning framework, named "Logic Network Flow," that integrates temporal logic specifications into mixed-integer programs for efficient robot planning. Inspired by the Graph-of-Convex-Sets formulation, temporal predicates are encoded as polyhedral constraints on each edge of a network flow model, instead of as constraints between nodes in traditional Logic Tree formulations. We further propose a network-flow-based Fourier-Motzkin elimination procedure that removes continuous flow variables while preserving convex relaxation tightness, leading to provably tighter convex relaxations and fewer constraints than Logic Tree formulations. For temporal logic motion planning with piecewise-affine dynamical systems, comprehensive experiments across vehicle routing, multi-robot coordination, and temporal logic control on dynamical systems using point-mass and linear inverted pendulum models demonstrate computational speedups of up to several orders of magnitude, alongside reduced memory consumption. Hardware demonstrations with quadrupedal robots validate real-time replanning capabilities under dynamically changing environmental conditions. The project website is at https://logicnetworkflow.github.io/.

cs.RO↗
arXiv2025

INSEva: A Comprehensive Chinese Benchmark for Large Language Models in Insurance

Insurance, as a critical component of the global financial system, demands high standards of accuracy and reliability in AI applications. While existing benchmarks evaluate AI capabilities across various domains, they often fail to capture the unique characteristics and requirements of the insurance domain. To address this gap, we present INSEva, a comprehensive Chinese benchmark specifically designed for evaluating AI systems' knowledge and capabilities in insurance. INSEva features a multi-dimensional evaluation taxonomy covering business areas, task formats, difficulty levels, and cognitive-knowledge dimension, comprising 38,704 high-quality evaluation examples sourced from authoritative materials. Our benchmark implements tailored evaluation methods for assessing both faithfulness and completeness in open-ended responses. Through extensive evaluation of 8 state-of-the-art Large Language Models (LLMs), we identify significant performance variations across different dimensions. While general LLMs demonstrate basic insurance domain competency with average scores above 80, substantial gaps remain in handling complex, real-world insurance scenarios. The benchmark will be public soon.

cs.CL↗
arXiv2025

Accelerating Signal-Temporal-Logic-Based Task and Motion Planning of Bipedal Navigation using Benders Decomposition

Task and motion planning under Signal Temporal Logic constraints is known to be NP-hard. A common class of approaches formulates these hybrid problems, which involve discrete task scheduling and continuous motion planning, as mixed-integer programs (MIP). However, in applications for bipedal locomotion, introduction of non-convex constraints such as kinematic reachability and footstep rotation exacerbates the computational complexity of MIPs. In this work, we present a method based on Benders Decomposition to address scenarios where solving the entire monolithic optimization problem is prohibitively intractable. Benders Decomposition proposes an iterative cutting-plane technique that partitions the problem into a master problem to prototype a plan that meets the task specification, and a series of subproblems for kinematics and dynamics feasibility checks. Our experiments demonstrate that this method achieves faster planning compared to alternative algorithms for solving the resulting optimization program with nonlinear constraints.

cs.RO↗
arXiv2025

AttriLens-Mol: Attribute Guided Reinforcement Learning for Molecular Property Prediction with Large Language Models

Large Language Models (LLMs) have shown promise in assisting molecular property prediction tasks but often rely on human-crafted prompts and chain-of-thought templates. While recent advanced large reasoning models like DeepSeek-R1 employ reinforcement learning for an extended ``thinking'' process, their reasoning can be verbose and lack relevance. We introduce AttriLens-Mol, an attribute-guided reinforcement learning framework for molecular property prediction with LLMs. AttriLens-Mol steers the model's reasoning by using: (1) a format reward encouraging attribute-based structured output, (2) a count reward to avoid enumerating irrelevant attributes, and (3) a rationality reward using advanced LLMs and RDKit to verify the relatedness of the generated attributes. This approach implicitly elicits the model's inherent knowledge of relevant molecular attributes during reasoning, enables making predictions for the molecular property more effectively. Experiments on both in-distribution and out-of-distribution datasets show that, training both 7B-size R1-Distilled-Qwen2.5 and R1-Distilled-LLaMA3.1 models on 4,000 samples with our proposed AttriLens-Mol method significantly boosts the performance, getting comparable or better results than supervised fine-tuning models (Mol-Instructions, ChemDFM, etc.) and advanced models (GPT-3.5, GPT-4o, DeepSeek-V3, DeepSeek-R1, etc.). Further, our extracted attributes for the target property, when used as features for an interpretable decision tree model, yield superior performance compared to attributes generated by prompting LLMs. This shows that AttriLens-Mol effectively elicits more relevant and predictive molecular attributes, leading to enhanced interpretability and performance for property prediction. We release the code in https://github.com/szu-tera/AttriLens-Mol.

cs.LG↗
arXiv2025

DynamicDTA: Drug-Target Binding Affinity Prediction Using Dynamic Descriptors and Graph Representation

Predicting drug-target binding affinity (DTA) is essential for identifying potential therapeutic candidates in drug discovery. However, most existing models rely heavily on static protein structures, often overlooking the dynamic nature of proteins, which is crucial for capturing conformational flexibility that will be beneficial for protein binding interactions. We introduce DynamicDTA, an innovative deep learning framework that incorporates static and dynamic protein features to enhance DTA prediction. The proposed DynamicDTA takes three types of inputs, including drug sequence, protein sequence, and dynamic descriptors. A molecular graph representation of the drug sequence is generated and subsequently processed through graph convolutional network, while the protein sequence is encoded using dilated convolutions. Dynamic descriptors, such as root mean square fluctuation, are processed through a multi-layer perceptron. These embedding features are fused with static protein features using cross-attention, and a tensor fusion network integrates all three modalities for DTA prediction. Extensive experiments on three datasets demonstrate that DynamicDTA achieves by at least 3.4% improvement in RMSE score with comparison to seven state-of-the-art baseline methods. Additionally, predicting novel drugs for Human Immunodeficiency Virus Type 1 and visualizing the docking complexes further demonstrates the reliability and biological relevance of DynamicDTA.

cs.RO↗
arXiv2025

Enhancing Chemical Reaction and Retrosynthesis Prediction with Large Language Model and Dual-task Learning

Chemical reaction and retrosynthesis prediction are fundamental tasks in drug discovery. Recently, large language models (LLMs) have shown potential in many domains. However, directly applying LLMs to these tasks faces two major challenges: (i) lacking a large-scale chemical synthesis-related instruction dataset; (ii) ignoring the close correlation between reaction and retrosynthesis prediction for the existing fine-tuning strategies. To address these challenges, we propose ChemDual, a novel LLM framework for accurate chemical synthesis. Specifically, considering the high cost of data acquisition for reaction and retrosynthesis, ChemDual regards the reaction-and-retrosynthesis of molecules as a related recombination-and-fragmentation process and constructs a large-scale of 4.4 million instruction dataset. Furthermore, ChemDual introduces an enhanced LLaMA, equipped with a multi-scale tokenizer and dual-task learning strategy, to jointly optimize the process of recombination and fragmentation as well as the tasks between reaction and retrosynthesis prediction. Extensive experiments on Mol-Instruction and USPTO-50K datasets demonstrate that ChemDual achieves state-of-the-art performance in both predictions of reaction and retrosynthesis, outperforming the existing conventional single-task approaches and the general open-source LLMs. Through molecular docking analysis, ChemDual generates compounds with diverse and strong protein binding affinity, further highlighting its strong potential in drug design.

cs.LG↗
arXiv2024

Property Enhanced Instruction Tuning for Multi-task Molecule Generation with Large Language Models

Large language models (LLMs) are widely applied in various natural language processing tasks such as question answering and machine translation. However, due to the lack of labeled data and the difficulty of manual annotation for biochemical properties, the performance for molecule generation tasks is still limited, especially for tasks involving multi-properties constraints. In this work, we present a two-step framework PEIT (\textbf{P}roperty \textbf{E}nhanced \textbf{I}nstruction \textbf{T}uning) to improve LLMs for molecular-related tasks. In the first step, we use textual descriptions, SMILES, and biochemical properties as multimodal inputs to pre-train a model called PEIT-GEN, by aligning multi-modal representations to synthesize instruction data. In the second step, we fine-tune existing open-source LLMs with the synthesized data, the resulting PEIT-LLM can handle molecule captioning, text-based molecule generation, molecular property prediction, and our newly proposed multi-constraint molecule generation tasks. Experimental results show that our pre-trained PEIT-GEN outperforms MolT5, BioT5, MolCA and Text+Chem-T5 in molecule captioning, demonstrating modalities align well between textual descriptions, structures, and biochemical properties. Furthermore, PEIT-LLM shows promising improvements in multi-task molecule generation, demonstrating the effectiveness of the PEIT framework for molecular tasks. The code and appendix are available at https://github.com/chenlong164/PEIT.

cs.AI↗
arXiv2024

S$^2$DN: Learning to Denoise Unconvincing Knowledge for Inductive Knowledge Graph Completion

Inductive Knowledge Graph Completion (KGC) aims to infer missing facts between newly emerged entities within knowledge graphs (KGs), posing a significant challenge. While recent studies have shown promising results in inferring such entities through knowledge subgraph reasoning, they suffer from (i) the semantic inconsistencies of similar relations, and (ii) noisy interactions inherent in KGs due to the presence of unconvincing knowledge for emerging entities. To address these challenges, we propose a Semantic Structure-aware Denoising Network (S$^2$DN) for inductive KGC. Our goal is to learn adaptable general semantics and reliable structures to distill consistent semantic knowledge while preserving reliable interactions within KGs. Specifically, we introduce a semantic smoothing module over the enclosing subgraphs to retain the universal semantic knowledge of relations. We incorporate a structure refining module to filter out unreliable interactions and offer additional knowledge, retaining robust structure surrounding target links. Extensive experiments conducted on three benchmark KGs demonstrate that S$^2$DN surpasses the performance of state-of-the-art models. These results demonstrate the effectiveness of S$^2$DN in preserving semantic consistency and enhancing the robustness of filtering out unreliable interactions in contaminated KGs.

cs.LG↗
arXiv2024

Y-Mol: A Multiscale Biomedical Knowledge-Guided Large Language Model for Drug Development

Large Language Models (LLMs) have recently demonstrated remarkable performance in general tasks across various fields. However, their effectiveness within specific domains such as drug development remains challenges. To solve these challenges, we introduce \textbf{Y-Mol}, forming a well-established LLM paradigm for the flow of drug development. Y-Mol is a multiscale biomedical knowledge-guided LLM designed to accomplish tasks across lead compound discovery, pre-clinic, and clinic prediction. By integrating millions of multiscale biomedical knowledge and using LLaMA2 as the base LLM, Y-Mol augments the reasoning capability in the biomedical domain by learning from a corpus of publications, knowledge graphs, and expert-designed synthetic data. The capability is further enriched with three types of drug-oriented instructions: description-based prompts from processed publications, semantic-based prompts for extracting associations from knowledge graphs, and template-based prompts for understanding expert knowledge from biomedical tools. Besides, Y-Mol offers a set of LLM paradigms that can autonomously execute the downstream tasks across the entire process of drug development, including virtual screening, drug design, pharmacological properties prediction, and drug-related interaction prediction. Our extensive evaluations of various biomedical sources demonstrate that Y-Mol significantly outperforms general-purpose LLMs in discovering lead compounds, predicting molecular properties, and identifying drug interaction events.

cs.AI↗