arXiv subjects

Junkai Ji

Publications and source records attributed to Junkai Ji.

At least 19 recordsLinked to original sources

arXiv2026

DegradeQuery: Counterfactual Tuple Pretraining for Context-Aware PROTAC Degradation Prediction

Proteolysis-targeting chimeras (PROTACs) induce protein degradation by recruiting a target protein to an E3 ubiquitin ligase, making degradation a joint outcome of the degrader molecule and its biological context. Although public databases contain thousands of structured molecule-target-E3 records, degradation measurements are available for only a small fraction of them. Existing supervised approaches therefore leave most recorded chemical-biological relationships unused. We introduce DegradeQuery, a context-aware prediction framework that converts these label-missing records into a pretraining signal. Its counterfactual tuple pretraining objective contrasts recorded tuples with alternatives formed by replacing the target, the E3 ligase, or both, enabling the model to learn contextual associations without assigning activity pseudo-labels. The resulting representation is then fine-tuned to predict degradation from the complete molecule-target-E3 context. On the official PROTAC-8K benchmark, DegradeQuery achieves an area under the receiver operating characteristic curve of 0.9065 and an accuracy of 0.8500, outperforming the compared methods. Controlled analyses further show that the improvement is primarily attributable to tuple-level pretraining, can be recovered using only label-missing records, and remains complementary to protein language model representations. These findings demonstrate that incompletely labeled PROTAC databases contain useful relational supervision and provide a practical route for learning context-aware degradation predictors from scarce experimental labels.

q-bio.BM↗

arXiv2026

SyncPlan: Long-Horizon LLM Coordination with Explicit Synchronization and Adaptive Correction

LLM-based multi-agent coordination faces a fundamental trade-off between efficiency and adaptivity in dynamic environments. Existing approaches typically rely on repeated LLM invocations or multi-round communication to adapt decisions during execution, introducing substantial latency and making coordination vulnerable to asynchronous progress and environmental changes. Conversely, one-shot planning reduces coordination overhead but produces open-loop plans that can quickly become stale or fail when actions depend on other agents and the environment. We introduce SyncPlan, a plan-execute-correct framework for long-horizon coordination through explicit synchronization and adaptive correction. Given the state and team-level task, a centralized LLM coordinator generates per-agent action chains in a single planning call. During execution, explicit wait primitives and deadlock detection enforce inter-agent and agent-environment dependencies, while a lightweight Plan Staleness Detector continuously assesses the remaining plan and triggers replanning when environmental changes invalidate its assumptions. We further optimize the coordinator through SFT and planning-oriented RL with dense task progress and outcome-level execution feedback. Experiments on the public Overcooked benchmark and the complex Honor of Kings environment show that SyncPlan achieves state-of-the-art task success rates while using less than 0.05% of the wall-clock runtime compared with existing LLM-based coordinators. Code and datasets will be made publicly available.

cs.RO↗

arXiv2026

SLSREC: Self-Supervised Contrastive Learning for Adaptive Fusion of Long- and Short-Term User Interests

User interests typically encompass both long-term preferences and short-term intentions, reflecting the dynamic nature of user behaviors across different timeframes. The uneven temporal distribution of user interactions highlights the evolving patterns of interests, making it challenging to accurately capture shifts in interests using comprehensive historical behaviors. To address this, we propose SLSRec, a novel Session-based model with the fusion of Long- and Short-term Recommendations that effectively captures the temporal dynamics of user interests by segmenting historical behaviors over time. Unlike conventional models that combine long- and short-term user interests into a single representation, compromising recommendation accuracy, SLSRec utilizes a self-supervised learning framework to disentangle these two types of interests. A contrastive learning strategy is introduced to ensure accurate calibration of long- and short-term interest representations. Additionally, an attention-based fusion network is designed to adaptively aggregate interest representations, optimizing their integration to enhance recommendation performance. Extensive experiments on three public benchmark datasets demonstrate that SLSRec consistently outperforms state-of-the-art models while exhibiting superior robustness across various scenarios.We will release all source code upon acceptance.

cs.IR↗

arXiv2026

Learning Task-Invariant Properties via Dreamer: Enabling Efficient Policy Transfer for Quadruped Robots

Achieving quadruped robot locomotion across diverse and dynamic terrains presents significant challenges, primarily due to the discrepancies between simulation environments and real-world conditions. Traditional sim-to-real transfer methods often rely on manual feature design or costly real-world fine-tuning. To address these limitations, this paper proposes the DreamTIP framework, which incorporates Task-Invariant Properties learning within the Dreamer world model architecture to enhance sim-to-real transfer capabilities. Guided by large language models, DreamTIP identifies and leverages Task-Invariant Properties, such as contact stability and terrain clearance, which exhibit robustness to dynamic variations and strong transferability across tasks. These properties are integrated into the world model as auxiliary prediction targets, enabling the policy to learn representations that are insensitive to underlying dynamic changes. Furthermore, an efficient adaptation strategy is designed, employing a mixed replay buffer and regularization constraints to rapidly calibrate to real-world dynamics while effectively mitigating representation collapse and catastrophic forgetting. Extensive experiments on complex terrains, including Stair, Climb, Tilt, and Crawl, demonstrate that DreamTIP significantly outperforms state-of-the-art baselines in both simulated and real-world environments. Our method achieves an average performance improvement of 28.1% across eight distinct simulated transfer tasks. In the real-world Climb task, the baseline method achieved only a 10\ success rate, whereas our method attained a 100% success rate. These results indicate that incorporating Task-Invariant Properties into Dreamer learning offers a novel solution for achieving robust and transferable robot locomotion.

cs.RO↗

arXiv2026

PreferRec: Learning and Transferring Pareto Preferences for Multi-objective Re-ranking

Multi-objective re-ranking has become a critical component of modern multi-stage recommender systems, as it tasked to balance multiple conflicting objectives such as accuracy, diversity, and fairness. Existing multi-objective re-ranking methods typically optimize aggregate objectives at the item level using static or handcrafted preference weights. This design overlooks that users inherently exhibit Pareto-optimal preferences at the intent level, reflecting personalized trade-offs among objectives rather than fixed weight combinations. Moreover, most approaches treat re-ranking task for each user as an isolated problem, and repeatedly learn the preferences from scratch. Such a paradigm not only incurs high computational cost, but also ignores the fact that users often share similar preference trade-off structures across objectives. Inspired by the existence of homogeneous multi-objective optimization spaces where Pareto-optimal patterns are transferable, we propose PreferRec, a novel framework that explicitly models and transfers Pareto preferences across users. Specifically, PreferRec is built upon three tightly coupled components: Preference-Aware Pareto Learning aims to capture user intrinsic trade-offs among multiple conflicting objectives at the intent level. By learning Pareto preference representations from re-ranking populations, this component explicitly models how users prioritize different objectives under diverse contexts. Knowledge-Guided Transfer facilitates efficient cross-user knowledge transfer by distilling shared optimization patterns across homogeneous optimization spaces. The transferred knowledge is then used to guide solution selection and personalized re-ranking, biasing the optimization process toward high-quality regions of the Pareto front while preserving user-specific preference characteristics.

cs.IR↗

arXiv2026

BioLM-Score: Language-Prior Conditioned Probabilistic Geometric Potentials for Protein-Ligand Scoring

Protein-ligand scoring is a central component of structure-based drug design, underpinning molecular docking, virtual screening, and pose optimization. Conventional physics-based energy functions are often computationally expensive, limiting their utility in large-scale screening. In contrast, deep learning-based scoring models offer improved computational efficiency but frequently suffer from limited cross-target generalization and poor interpretability, which restrict their practical applicability. Here we present BioLM-Score, a simple yet generalizable protein-ligand scoring model that couples geometric modeling with representation learning. Specifically, it employs modality-specific and structure-aware encoders for proteins and ligands, each augmented with biomolecular language models to enrich structural and chemical representations. Subsequently, these representations are integrated through a mixture density network to predict multimodal interatomic distance distributions, from which statistically grounded likelihood-based scores are derived. Evaluations on the CASF-2016 benchmark demonstrate that BioLM-Score achieves significant improvements across docking, scoring, ranking, and screening tasks. Moreover, the proposed scoring function serves as an effective optimization objective for guiding docking protocols and conformational search. In summary, BioLM-Score provides a principled and practical alternative to existing scoring functions, combining efficiency, generalization, and interpretability for structure-based drug discovery.

q-bio.BM↗

arXiv2026

RIGA-Fold: A General Framework for Protein Inverse Folding via Recurrent Interaction and Geometric Awareness

Protein inverse folding, the task of predicting amino acid sequences for desired structures, is pivotal for de novo protein design. However, existing GNN-based methods typically suffer from restricted receptive fields that miss long-range dependencies and a "single-pass" inference paradigm that leads to error accumulation. To address these bottlenecks, we propose RIGA-Fold, a framework that synergizes Recurrent Interaction with Geometric Awareness. At the micro-level, we introduce a Geometric Attention Update (GAU) module where edge features explicitly serve as attention keys, ensuring strictly SE(3)-invariant local encoding. At the macro-level, we design an attention-based Global Context Bridge that acts as a soft gating mechanism to dynamically inject global topological information. Furthermore, to bridge the gap between structural and sequence modalities, we introduce an enhanced variant, RIGA-Fold*, which integrates trainable geometric features with frozen evolutionary priors from ESM-2 and ESM-IF via a dual-stream architecture. Finally, a biologically inspired ``predict-recycle-refine'' strategy is implemented to iteratively denoise sequence distributions. Extensive experiments on CATH 4.2, TS50, and TS500 benchmarks demonstrate that our geometric framework is highly competitive, while RIGA-Fold* significantly outperforms state-of-the-art baselines in both sequence recovery and structural consistency.

cs.LG↗

arXiv2026

Unveiling Scaling Behaviors in Molecular Language Models: Effects of Model Size, Data, and Representation

Molecular generative models, often employing GPT-style language modeling on molecular string representations, have shown promising capabilities when scaled to large datasets and model sizes. However, it remains unclear and subject to debate whether these models adhere to predictable scaling laws under fixed computational budgets, which is a crucial understanding for optimally allocating resources between model size, data volume, and molecular representation. In this study, we systematically investigate the scaling behavior of molecular language models across both pretraining and downstream tasks. We train 300 models and conduct over 10,000 experiments, rigorously controlling compute budgets while independently varying model size, number of training tokens, and molecular representation. Our results demonstrate clear scaling laws in molecular models for both pretraining and downstream transfer, reveal the substantial impact of molecular representation on performance, and explain previously observed inconsistencies in scaling behavior for molecular generation. Additionally, we publicly release the largest library of molecular language models to date to facilitate future research and development. Code and models are available at https://github.com/SZU-ADDG/MLM-Scaling.

cs.LG↗

arXiv2026

From Tokens to Blocks: A Block-Diffusion Perspective on Molecular Generation

Drug discovery can be viewed as a combinatorial search over an immense chemical space, motivating the development of deep generative models for de novo molecular design. Among these, GPT-based molecular language models (MLM) have shown strong molecular design performance by learning chemical syntax and semantics from large-scale data. However, existing MLMs face two fundamental limitations: they inadequately capture the graph-structured nature of molecules when formulated as next-token prediction problems, and they typically lack explicit mechanisms for target-aware generation. Here, we propose SoftMol, a unified framework that co-designs molecular representation, model architecture, and search strategy for target-aware molecular generation. SoftMol introduces soft fragments, a rule-free block representation of SMILES that enables diffusion-native modeling, and develops SoftBD, the first block-diffusion molecular language model that combines local bidirectional diffusion with autoregressive generation under molecular structural constraints. To favor generated molecules with high drug-likeness and synthetic accessibility, SoftBD is trained on a carefully curated dataset named ZINC-Curated. SoftMol further integrates a gated Monte Carlo tree search to assemble fragments in a target-aware manner. Experimental results show that, compared with current state-of-the-art models, SoftMol achieves 100% chemical validity, improves binding affinity by 9.7%, yields a 2-3x increase in molecular diversity, and delivers a 6.6x speedup in inference efficiency. Code is available at https://github.com/szu-aicourse/softmol

cs.LG↗

arXiv2026

Rethinking Drug-Drug Interaction Modeling as Generalizable Relation Learning

Drug-drug interaction (DDI) prediction is central to drug discovery and clinical development, particularly in the context of increasingly prevalent polypharmacy. Although existing computational methods achieve strong performance on standard benchmarks, they often fail to generalize to realistic deployment scenarios, where most candidate drug pairs involve previously unseen drugs and validated interactions are scarce. We demonstrate that proximity in the embedding spaces of prevailing molecule-centric DDI models does not reliably correspond to interaction labels, and that simply scaling up model capacity therefore fails to improve generalization. To address these limitations, we propose GenRel-DDI, a generalizable relation learning framework that reformulates DDI prediction as a relation-centric learning problem, in which interaction representations are learned independently of drug identities. This relation-level abstraction enables the capture of transferable interaction patterns that generalize to unseen drugs and novel drug pairs. Extensive experiments across multiple benchmark demonstrate that GenRel-DDI consistently and significantly outperforms state-of-the-art methods, with particularly large gains on strict entity-disjoint evaluations, highlighting the effectiveness and practical utility of relation learning for robust DDI prediction. The code is available at https://github.com/SZU-ADDG/GenRel-DDI.

cs.LG↗

arXiv2025

Toward Closed-loop Molecular Discovery via Language Model, Property Alignment and Strategic Search

Drug discovery is a time-consuming and expensive process, with traditional high-throughput and docking-based virtual screening hampered by low success rates and limited scalability. Recent advances in generative modelling, including autoregressive, diffusion, and flow-based approaches, have enabled de novo ligand design beyond the limits of enumerative screening. Yet these models often suffer from inadequate generalization, limited interpretability, and an overemphasis on binding affinity at the expense of key pharmacological properties, thereby restricting their translational utility. Here we present Trio, a molecular generation framework integrating fragment-based molecular language modeling, reinforcement learning, and Monte Carlo tree search, for effective and interpretable closed-loop targeted molecular design. Through the three key components, Trio enables context-aware fragment assembly, enforces physicochemical and synthetic feasibility, and guides a balanced search between the exploration of novel chemotypes and the exploitation of promising intermediates within protein binding pockets. Experimental results show that Trio reliably achieves chemically valid and pharmacologically enhanced ligands, outperforming state-of-the-art approaches with improved binding affinity (+7.85%), drug-likeness (+11.10%) and synthetic accessibility (+12.05%), while expanding molecular diversity more than fourfold. By combining generalization, plausibility, and interpretability, Trio establishes a closed-loop generative paradigm that redefines how chemical space can be navigated, offering a transformative foundation for the next era of AI-driven drug discovery.

cs.AI↗

arXiv2025

FROGENT: An End-to-End Full-process Drug Design Multi-Agent System

Drug discovery is a complex, multi-step pipeline that remains heavily dependent on manual, experience-driven operations; meanwhile, existing customized artificial intelligence tools are fragmented across web applications, desktop software, and code libraries, resulting in incompatible interfaces and inefficient, burdensome workflows. To overcome these challenges, we propose FROGENT, a full-process drug design multi-agent system that leverages the planning, reasoning, and tool-use capabilities of large language models (LLMs) to unify drug discovery within a closed-loop and autonomous framework. FROGENT is a collaborative multi-agent system comprising a central Orchestrate Agent for strategic workflow coordination and three distributed agents, Retrieve, Forge, and Gauge, that employ dynamic biochemical databases, extensible tool libraries, and task-specific computational models via the Model Context Protocol. This architecture enables end-to-end execution of complex drug discovery pipelines, covering target identification, small-molecule generation, peptide optimization, and retrosynthetic planning. Across eight benchmarks spanning core drug discovery tasks, FROGENT consistently outperforms six increasingly advanced ReAct-style agents. Case studies further demonstrate its practicality and generalization across real-world small-molecule and peptide design scenarios. Overall, FROGENT not only achieves substantial gains in efficiency and accuracy, but also demonstrates the potential of LLM-based agentic systems to autonomously orchestrate drug development pipelines, reducing, or even replacing, reliance on manual, experience-driven human intervention.

q-bio.BM↗

arXiv2025

IBEX: Information-Bottleneck-EXplored Coarse-to-Fine Molecular Generation under Limited Data

Three-dimensional generative models increasingly drive structure-based drug discovery, yet it remains constrained by the scarce publicly available protein-ligand complexes. Under such data scarcity, almost all existing pipelines struggle to learn transferable geometric priors and consequently overfit to training-set biases. As such, we present IBEX, an Information-Bottleneck-EXplored coarse-to-fine pipeline to tackle the chronic shortage of protein-ligand complex data in structure-based drug design. Specifically, we use PAC-Bayesian information-bottleneck theory to quantify the information density of each sample. This analysis reveals how different masking strategies affect generalization and indicates that, compared with conventional de novo generation, the constrained Scaffold Hopping task endows the model with greater effective capacity and improved transfer performance. IBEX retains the original TargetDiff architecture and hyperparameters for training to generate molecules compatible with the binding pocket; it then applies an L-BFGS optimization step to finely refine each conformation by optimizing five physics-based terms and adjusting six translational and rotational degrees of freedom in under one second. With only these modifications, IBEX raises the zero-shot docking success rate on CBGBench CrossDocked2020-based from 53% to 64%, improves the mean Vina score from $-7.41 kcal mol^{-1}$ to $-8.07 kcal mol^{-1}$, and achieves the best median Vina energy in 57 of 100 pockets versus 3 for the original TargetDiff. IBEX also increases the QED by 25%, achieves state-of-the-art validity and diversity, and markedly reduces extrapolation error.

cs.LG↗

arXiv2025

MODA: A Unified 3D Diffusion Framework for Multi-Task Target-Aware Molecular Generation

Three-dimensional molecular generators based on diffusion models can now reach near-crystallographic accuracy, yet they remain fragmented across tasks. SMILES-only inputs, two-stage pretrain-finetune pipelines, and one-task-one-model practices hinder stereochemical fidelity, task alignment, and zero-shot transfer. We introduce MODA, a diffusion framework that unifies fragment growing, linker design, scaffold hopping, and side-chain decoration with a Bayesian mask scheduler. During training, a contiguous spatial fragment is masked and then denoised in one pass, enabling the model to learn shared geometric and chemical priors across tasks. Multi-task training yields a universal backbone that surpasses six diffusion baselines and three training paradigms on substructure, chemical property, interaction, and geometry. Model-C reduces ligand-protein clashes and substructure divergences while maintaining Lipinski compliance, whereas Model-B preserves similarity but trails in novelty and binding affinity. Zero-shot de novo design and lead-optimisation tests confirm stable negative Vina scores and high improvement rates without force-field refinement. These results demonstrate that a single-stage multi-task diffusion routine can replace two-stage workflows for structure-based molecular design.

q-bio.BM↗

arXiv2025

READ: A Retrieval-Alignment Diffusion Framework for Structure-based Drug Design

Structure-based drug design (SBDD) models are central to modern pharmaceutical research, enabling the rational exploration of protein-ligand interactions at atomic resolution. However, most existing approaches frame molecular generation as an isolated optimization or a one-to-one matching task, overlooking the shared binding patterns and intrinsic similarities among protein-ligand complexes. This fragmented perspective constrains their ability to capture the fundamental principles governing molecular recognition and binding specificity. Moreover, the limited availability of high-quality experimental data further hampers model generalization and real-world applicability. To address these challenges, we present READ, a retrieval-alignment molecular generation framework that conditions the generative process on small molecules targeting homologous proteins. Retrieved ligands are aligned with a diffusion model across multiple representational spaces and integrated as conditional guidance throughout successive stages of generation. Under a standardized docking-based evaluation protocol, READ achieves consistently strong performance against state-of-the-art SBDD methods. More importantly, it introduces a retrieval-alignment paradigm for structure-based molecular generation, offering a practical framework for early-stage computational hit generation while leaving prospective experimental validation as future work.

q-bio.BM↗

arXiv2025

UINO-FSS: Unifying Representation Learning and Few-shot Segmentation via Hierarchical Distillation and Mamba-HyperCorrelation

Few-shot semantic segmentation has attracted growing interest for its ability to generalize to novel object categories using only a few annotated samples. To address data scarcity, recent methods incorporate multiple foundation models to improve feature transferability and segmentation performance. However, they often rely on dual-branch architectures that combine pre-trained encoders to leverage complementary strengths, a design that limits flexibility and efficiency. This raises a fundamental question: can we build a unified model that integrates knowledge from different foundation architectures? Achieving this is, however, challenging due to the misalignment between class-agnostic segmentation capabilities and fine-grained discriminative representations. To this end, we present UINO-FSS, a novel framework built on the key observation that early-stage DINOv2 features exhibit distribution consistency with SAM's output embeddings. This consistency enables the integration of both models' knowledge into a single-encoder architecture via coarse-to-fine multimodal distillation. In particular, our segmenter consists of three core components: a bottleneck adapter for embedding alignment, a meta-visual prompt generator that leverages dense similarity volumes and semantic embeddings, and a mask decoder. Using hierarchical cross-model distillation, we effectively transfer SAM's knowledge into the segmenter, further enhanced by Mamba-based 4D correlation mining on support-query pairs. Extensive experiments on PASCAL-5$^i$ and COCO-20$^i$ show that UINO-FSS achieves new state-of-the-art results under the 1-shot setting, with mIoU of 80.6 (+3.8%) on PASCAL-5$^i$ and 64.5 (+4.1%) on COCO-20$^i$, demonstrating the effectiveness of our unified approach.

cs.CV↗

arXiv2025

A Dual-Directional Context-Aware Test-Time Learning for Text Classification

Text classification assigns text to predefined categories. Traditional methods struggle with complex structures and long-range dependencies. Deep learning with recurrent neural networks and Transformer models has improved feature extraction and context awareness. However, these models still trade off interpretability, efficiency and contextual range. We propose the Dynamic Bidirectional Elman Attention Network (DBEAN). DBEAN combines bidirectional temporal modeling and self-attention. It dynamically weights critical input segments and preserves computational efficiency.

cs.CL↗

arXiv2024

Dockformer: A transformer-based molecular docking paradigm for large-scale virtual screening

Molecular docking is a crucial step in drug development, which enables the virtual screening of compound libraries to identify potential ligands that target proteins of interest. However, the computational complexity of traditional docking models increases as the size of the compound library increases. Recently, deep learning algorithms can provide data-driven research and development models to increase the speed of the docking process. Unfortunately, few models can achieve superior screening performance compared to that of traditional models. Therefore, a novel deep learning-based docking approach named Dockformer is introduced in this study. Dockformer leverages multimodal information to capture the geometric topology and structural knowledge of molecules and can directly generate binding conformations with the corresponding confidence measures in an end-to-end manner. The experimental results show that Dockformer achieves success rates of 90.53% and 82.71% on the PDBbind core set and PoseBusters benchmarks, respectively, and more than a 100-fold increase in the inference process speed, outperforming almost all state-of-the-art docking methods. In addition, the ability of Dockformer to identify the main protease inhibitors of coronaviruses is demonstrated in a real-world virtual screening scenario. Considering its high docking accuracy and screening efficiency, Dockformer can be regarded as a powerful and robust tool in the field of drug design.

cs.LG↗