arXiv subjects

Hongxin Xiang

Publications and source records attributed to Hongxin Xiang.

14 recordsLinked to original sources

arXiv2026

Towards Generalizable and Evidential Nuclear Magnetic Resonance-Based Molecular Structure Elucidation via Large Language Model Agent

Nuclear Magnetic Resonance (NMR) spectroscopy is the gold standard for molecular structure elucidation, yet interpreting complex spectra for unknown molecules remains a bottleneck reliant on human expertise. While artificial intelligence has advanced this field, current methods face a critical trade-off: database retrieval cannot identify novel scaffolds, while de novo molecular structure elucidation models operate as black boxes, lacking the atom-level interpretability required for rigorous scientific validation. Here, we present NMRAgent, an evidential reasoning agent powered by large language models (LLMs) that bridges this gap by integrating specialized spectral analysis tools with chemical knowledge graphs. Unlike previous approaches, NMRAgent mimics the deductive reasoning of human experts: it takes experimental NMR spectra and molecular formula as input, plans the elucidation process, proposes candidate structures, verifies peak-atom consistency, and refines misaligned substructure through formula-aware fragment optimization. Enabled by its evidential reasoning, NMRAgent outperforms state-of-the-art methods, improving top-1 accuracy by 46.5% and Tanimoto similarity by 0.502 on a scaffold-split benchmark with novel scaffolds in the test set. Besides, we demonstrate the agent's practical utility by elucidating the structures of two previously unknown natural products isolated from Hydrangea davidii and Vitex trifolia, and by correcting structural misassignments in established literature. By combining high-accuracy prediction with transparent and evidence-based reasoning, NMRAgent establishes a new paradigm for interpretable AI in analytical chemistry.

cs.LG↗

arXiv2026

A large-scale foundation model enables simulation-to-real adaptation for nuclear magnetic resonance-based molecular structure analysis

Nuclear Magnetic Resonance (NMR) spectroscopy is a powerful tool for molecular structure analysis, and spectral artificial intelligence offers great potential for its rapid and automated interpretation. However, the scarcity of experimental NMR datasets has constrained deep learning in this domain to narrow, task-specific applications that lack broad generalization. Here, we introduce UltraNMR, a large-scale foundation model for NMR that leverages the intrinsic properties of NMR spectra to learn generalizable spectral representations. We collected 158 million paired simulated $^{1}$H and $^{13}$C NMR spectra to train UltraNMR, employing multiple domain-specific pre-training objectives. UltraNMR captures both intra-spectral and inter-spectral dependencies, enabling seamless simulation-to-real adaptation. We demonstrate that adapting UltraNMR to a range of molecular structure analysis tasks on experimental NMR spectra consistently yields state-of-the-art performance and clearly outperforms UltraNMR variants trained directly on downstream data without simulation pre-training. We also construct a large-scale NMR spectral vector library by encoding simulated NMR spectra using UltraNMR, covering 94 million unique molecules and enabling effective structure-aware retrieval. In real-world applications, UltraNMR facilitates the structural elucidation of two previously unknown natural products from Chinese herbal medicines recorded in the Chinese Pharmacopoeia. These results suggest that large-scale simulation pre-training can effectively bridge the simulation-to-real gap, enabling robust and generalizable molecular structure analysis of real-world NMR spectra.

physics.chem-ph↗

arXiv2026

MemNovo: Look Back at the Spectrum for Balanced De Novo Peptide Sequencing from Mass Spectrometry

De novo peptide sequencing from tandem mass spectrometry is pivotal in proteomics, enabling identification of novel peptides without reference databases. While recent Transformer-based encoder-decoder models have achieved remarkable performance, we uncover a critical pathology in their inference dynamics. Through comprehensive feature scaling experiments, we demonstrate that existing auto-regressive peptide decoders tend to over-rely on generated-sequence priors while progressively under-utilizing fine-grained physical evidence from the input mass spectrum. This phenomenon leads to suboptimal results, where generated peptide sequences are biologically plausible yet not faithful to the input spectrum. To rectify this, we propose MemNovo, a training-free and plug-and-play mechanism that re-balances peptide and spectral contributions at inference time. MemNovo alleviates the information bottleneck by establishing a persistent spectral memory bank and injecting retrieved features directly into the final decoding stage via an ultra-conservative residual connection. Theoretical analysis confirms that this mechanism restores the mutual information between the decoder state and the raw spectrum. Extensive experiments on the Nine Species benchmark with two representative baselines, Casanovo and InstaNovo, demonstrate that MemNovo consistently improves both amino acid precision and peptide precision, achieving up to 39.1% relative improvement in peptide precision for Casanovo and up to 3.9% for InstaNovo, with negligible computational overhead.

cs.LG↗

arXiv2026

Refold: Refining Protein Inverse Folding with Efficient Structural Matching and Fusion

Protein inverse folding aims to design an amino acid sequence that will fold into a given backbone structure, serving as a central task in protein design. Two main paradigms have been widely explored. Template-based methods exploit database-derived structural priors and can achieve high local precision when close structural neighbors are available, but their dependence on database coverage and match quality often degrades performance on out-of-distribution (OOD) targets. Deep learning approaches, in contrast, learn general structure-to-sequence regularities and usually generalize better to new backbones. However, they struggle to capture fine-grained local structure, which can cause uncertain residue predictions and missed local motifs in ambiguous regions. We introduce Refold, a novel framework that synergistically integrates the strengths of database-derived structural priors and deep learning prediction to enhance inverse folding. Refold obtains structural priors from matched neighbors and fuses them with model predictions to refine residue probabilities. In practice, low-quality neighbors can introduce noise, potentially degrading model performance. We address this issue with a Dynamic Utility Gate that controls prior injection and falls back to the base prediction when the priors are untrustworthy. Comprehensive evaluations on standard benchmarks demonstrate that Refold achieves state-of-the-art native sequence recovery of 0.63 on both CATH 4.2 and CATH 4.3. Also, analysis indicates that Refold delivers larger gains on high-uncertainty regions, reflecting the complementarity between structural priors and deep learning predictions.

cs.LG↗

arXiv2026

Rethinking Genomic Modeling Through Optical Character Recognition

Recent genomic foundation models largely adopt large language model architectures that treat DNA as a one-dimensional token sequence. However, exhaustive sequential reading is structurally misaligned with sparse and discontinuous genomic semantics, leading to wasted computation on low-information background and preventing understanding-driven compression for long contexts. Here, we present OpticalDNA, a vision-based framework that reframes genomic modeling as Optical Character Recognition (OCR)-style document understanding. OpticalDNA renders DNA into structured visual layouts and trains an OCR-capable vision--language model with a visual DNA encoder and a document decoder, where the encoder produces compact, reconstructible visual tokens for high-fidelity compression. Building on this representation, OpticalDNA defines prompt-conditioned objectives over core genomic primitives-reading, region grounding, subsequence retrieval, and masked span completion-thereby learning layout-aware DNA representations that retain fine-grained genomic information under a reduced effective token budget. Across diverse genomic benchmarks, OpticalDNA consistently outperforms recent baselines; on sequences up to 450k bases, it achieves the best overall performance with nearly 20$\times$ fewer effective tokens, and surpasses models with up to 985$\times$ more activated parameters while tuning only 256k trainable parameters.

cs.CV↗

arXiv2025

ImageDDI: Image-enhanced Molecular Motif Sequence Representation for Drug-Drug Interaction Prediction

To mitigate the potential adverse health effects of simultaneous multi-drug use, including unexpected side effects and interactions, accurately identifying and predicting drug-drug interactions (DDIs) is considered a crucial task in the field of deep learning. Although existing methods have demonstrated promising performance, they suffer from the bottleneck of limited functional motif-based representation learning, as DDIs are fundamentally caused by motif interactions rather than the overall drug structures. In this paper, we propose an Image-enhanced molecular motif sequence representation framework for \textbf{DDI} prediction, called ImageDDI, which represents a pair of drugs from both global and local structures. Specifically, ImageDDI tokenizes molecules into functional motifs. To effectively represent a drug pair, their motifs are combined into a single sequence and embedded using a transformer-based encoder, starting from the local structure representation. By leveraging the associations between drug pairs, ImageDDI further enhances the spatial representation of molecules using global molecular image information (e.g. texture, shadow, color, and planar spatial relationships). To integrate molecular visual information into functional motif sequence, ImageDDI employs Adaptive Feature Fusion, enhancing the generalization of ImageDDI by dynamically adapting the fusion process of feature representations. Experimental results on widely used datasets demonstrate that ImageDDI outperforms state-of-the-art methods. Moreover, extensive experiments show that ImageDDI achieved competitive performance in both 2D and 3D image-enhanced scenarios compared to other models.

cs.CV↗

arXiv2025

ModuLM: Enabling Modular and Multimodal Molecular Relational Learning with Large Language Models

Molecular Relational Learning (MRL) aims to understand interactions between molecular pairs, playing a critical role in advancing biochemical research. With the recent development of large language models (LLMs), a growing number of studies have explored the integration of MRL with LLMs and achieved promising results. However, the increasing availability of diverse LLMs and molecular structure encoders has significantly expanded the model space, presenting major challenges for benchmarking. Currently, there is no LLM framework that supports both flexible molecular input formats and dynamic architectural switching. To address these challenges, reduce redundant coding, and ensure fair model comparison, we propose ModuLM, a framework designed to support flexible LLM-based model construction and diverse molecular representations. ModuLM provides a rich suite of modular components, including 8 types of 2D molecular graph encoders, 11 types of 3D molecular conformation encoders, 7 types of interaction layers, and 7 mainstream LLM backbones. Owing to its highly flexible model assembly mechanism, ModuLM enables the dynamic construction of over 50,000 distinct model configurations. In addition, we provide comprehensive results to demonstrate the effectiveness of ModuLM in supporting LLM-based MRL tasks.

cs.LG↗

arXiv2025

EDBench: Large-Scale Electron Density Data for Molecular Modeling

Existing molecular machine learning force fields (MLFFs) generally focus on the learning of atoms, molecules, and simple quantum chemical properties (such as energy and force), but ignore the importance of electron density (ED) $\rho(r)$ in accurately understanding molecular force fields (MFFs). ED describes the probability of finding electrons at specific locations around atoms or molecules, which uniquely determines all ground state properties (such as energy, molecular structure, etc.) of interactive multi-particle systems according to the Hohenberg-Kohn theorem. However, the calculation of ED relies on the time-consuming first-principles density functional theory (DFT) which leads to the lack of large-scale ED data and limits its application in MLFFs. In this paper, we introduce EDBench, a large-scale, high-quality dataset of ED designed to advance learning-based research at the electronic scale. Built upon the PCQM4Mv2, EDBench provides accurate ED data, covering 3.3 million molecules. To comprehensively evaluate the ability of models to understand and utilize electronic information, we design a suite of ED-centric benchmark tasks spanning prediction, retrieval, and generation. Our evaluation on several state-of-the-art methods demonstrates that learning from EDBench is not only feasible but also achieves high accuracy. Moreover, we show that learning-based method can efficiently calculate ED with comparable precision while significantly reducing the computational cost relative to traditional DFT calculations. All data and benchmarks from EDBench will be freely available, laying a robust foundation for ED-driven drug discovery and materials science.

physics.chem-ph↗

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

FlexMol: A Flexible Toolkit for Benchmarking Molecular Relational Learning

Molecular relational learning (MRL) is crucial for understanding the interaction behaviors between molecular pairs, a critical aspect of drug discovery and development. However, the large feasible model space of MRL poses significant challenges to benchmarking, and existing MRL frameworks face limitations in flexibility and scope. To address these challenges, avoid repetitive coding efforts, and ensure fair comparison of models, we introduce FlexMol, a comprehensive toolkit designed to facilitate the construction and evaluation of diverse model architectures across various datasets and performance metrics. FlexMol offers a robust suite of preset model components, including 16 drug encoders, 13 protein sequence encoders, 9 protein structure encoders, and 7 interaction layers. With its easy-to-use API and flexibility, FlexMol supports the dynamic construction of over 70, 000 distinct combinations of model architectures. Additionally, we provide detailed benchmark results and code examples to demonstrate FlexMol's effectiveness in simplifying and standardizing MRL model development and comparison.

cs.LG↗

arXiv2024

MaskMol: Knowledge-guided Molecular Image Pre-Training Framework for Activity Cliffs

Activity cliffs, which refer to pairs of molecules that are structurally similar but show significant differences in their potency, can lead to model representation collapse and make the model challenging to distinguish them. Our research indicates that as molecular similarity increases, graph-based methods struggle to capture these nuances, whereas image-based approaches effectively retain the distinctions. Thus, we developed MaskMol, a knowledge-guided molecular image self-supervised learning framework. MaskMol accurately learns the representation of molecular images by considering multiple levels of molecular knowledge, such as atoms, bonds, and substructures. By utilizing pixel masking tasks, MaskMol extracts fine-grained information from molecular images, overcoming the limitations of existing deep learning models in identifying subtle structural changes. Experimental results demonstrate MaskMol's high accuracy and transferability in activity cliff estimation and compound potency prediction across 20 different macromolecular targets, outperforming 25 state-of-the-art deep learning and machine learning approaches. Visualization analyses reveal MaskMol's high biological interpretability in identifying activity cliff-relevant molecular substructures. Notably, through MaskMol, we identified candidate EP4 inhibitors that could be used to treat tumors. This study not only raises awareness about activity cliffs but also introduces a novel method for molecular image representation learning and virtual screening, advancing drug discovery and providing new insights into structure-activity relationships (SAR).

cs.CV↗

arXiv2021

Class Knowledge Overlay to Visual Feature Learning for Zero-Shot Image Classification

New categories can be discovered by transforming semantic features into synthesized visual features without corresponding training samples in zero-shot image classification. Although significant progress has been made in generating high-quality synthesized visual features using generative adversarial networks, guaranteeing semantic consistency between the semantic features and visual features remains very challenging. In this paper, we propose a novel zero-shot learning approach, GAN-CST, based on class knowledge to visual feature learning to tackle the problem. The approach consists of three parts, class knowledge overlay, semi-supervised learning and triplet loss. It applies class knowledge overlay (CKO) to obtain knowledge not only from the corresponding class but also from other classes that have the knowledge overlay. It ensures that the knowledge-to-visual learning process has adequate information to generate synthesized visual features. The approach also applies a semi-supervised learning process to re-train knowledge-to-visual model. It contributes to reinforcing synthesized visual features generation as well as new category prediction. We tabulate results on a number of benchmark datasets demonstrating that the proposed model delivers superior performance over state-of-the-art approaches.

cs.CV↗

arXiv2021

Multi-Knowledge Fusion for New Feature Generation in Generalized Zero-Shot Learning

Suffering from the semantic insufficiency and domain-shift problems, most of existing state-of-the-art methods fail to achieve satisfactory results for Zero-Shot Learning (ZSL). In order to alleviate these problems, we propose a novel generative ZSL method to learn more generalized features from multi-knowledge with continuously generated new semantics in semantic-to-visual embedding. In our approach, the proposed Multi-Knowledge Fusion Network (MKFNet) takes different semantic features from multi-knowledge as input, which enables more relevant semantic features to be trained for semantic-to-visual embedding, and finally generates more generalized visual features by adaptively fusing visual features from different knowledge domain. The proposed New Feature Generator (NFG) with adaptive genetic strategy is used to enrich semantic information on the one hand, and on the other hand it greatly improves the intersection of visual feature generated by MKFNet and unseen visual faetures. Empirically, we show that our approach can achieve significantly better performance compared to existing state-of-the-art methods on a large number of benchmarks for several ZSL tasks, including traditional ZSL, generalized ZSL and zero-shot retrieval.

cs.CV↗

arXiv2021

Cross Knowledge-based Generative Zero-Shot Learning Approach with Taxonomy Regularization

Although zero-shot learning (ZSL) has an inferential capability of recognizing new classes that have never been seen before, it always faces two fundamental challenges of the cross modality and crossdomain challenges. In order to alleviate these problems, we develop a generative network-based ZSL approach equipped with the proposed Cross Knowledge Learning (CKL) scheme and Taxonomy Regularization (TR). In our approach, the semantic features are taken as inputs, and the output is the synthesized visual features generated from the corresponding semantic features. CKL enables more relevant semantic features to be trained for semantic-to-visual feature embedding in ZSL, while Taxonomy Regularization (TR) significantly improves the intersections with unseen images with more generalized visual features generated from generative network. Extensive experiments on several benchmark datasets (i.e., AwA1, AwA2, CUB, NAB and aPY) show that our approach is superior to these state-of-the-art methods in terms of ZSL image classification and retrieval.

cs.CV↗