Yusong Wang

Ailiang Lin, Zhuoyun Li, Yusong Wang et al.

Recent advances in Large Language Models (LLMs) have opened new avenues for generating training-free text embeddings. However, the causal attention in decoder-only LLMs prevents earlier tokens from attending to future context, leading to biased contextualized representations. In this work, we propose Reverse prompting with Explicit One-word Limitation (ReverseEOL), a simple yet effective method for enhancing the representational capability of frozen LLMs. ReverseEOL augments the standard forward embedding with an additional reversed embedding derived from the reversed input text. Since reversing the input exposes each token to context inaccessible in the original order, the resulting reversed embedding effectively provides complementary information to the original one. As a result, combining the forward and reversed embeddings yields a richer final representation. Comprehensive experiments on STS and MTEB benchmarks demonstrate that ReverseEOL significantly improves the performance of existing training-free baselines across a broad range of LLMs with diverse architectures and scales. Extensive ablations and analyses further confirm the necessity of our reversal mechanism.

Shaoning Li, Mingyu Li, Yusong Wang et al.

Investigating conformational landscapes of proteins is a crucial way to understand their biological functions and properties. AlphaFlow stands out as a sequence-conditioned generative model that introduces flexibility into structure prediction models by fine-tuning AlphaFold under the flow-matching framework. Despite the advantages of efficient sampling afforded by flow-matching, AlphaFlow still requires multiple runs of AlphaFold to finally generate one single conformation. Due to the heavy consumption of AlphaFold, its applicability is limited in sampling larger set of protein ensembles or the longer chains within a constrained timeframe. In this work, we propose a feature-conditioned generative model called AlphaFlow-Lit to realize efficient protein ensembles generation. In contrast to the full fine-tuning on the entire structure, we focus solely on the light-weight structure module to reconstruct the conformation. AlphaFlow-Lit performs on-par with AlphaFlow and surpasses its distilled version without pretraining, all while achieving a significant sampling acceleration of around 47 times. The advancement in efficiency showcases the potential of AlphaFlow-Lit in enabling faster and more scalable generation of protein ensembles.

Dongyuan Li, Yusong Wang, Kotaro Funakoshi et al.

Multimodal emotion recognition aims to recognize emotions for each utterance of multiple modalities, which has received increasing attention for its application in human-machine interaction. Current graph-based methods fail to simultaneously depict global contextual features and local diverse uni-modal features in a dialogue. Furthermore, with the number of graph layers increasing, they easily fall into over-smoothing. In this paper, we propose a method for joint modality fusion and graph contrastive learning for multimodal emotion recognition (Joyful), where multimodality fusion, contrastive learning, and emotion recognition are jointly optimized. Specifically, we first design a new multimodal fusion mechanism that can provide deep interaction and fusion between the global contextual and uni-modal specific features. Then, we introduce a graph contrastive learning framework with inter-view and intra-view contrastive losses to learn more distinguishable representations for samples with different sentiments. Extensive experiments on three benchmark datasets indicate that Joyful achieved state-of-the-art (SOTA) performance compared to all baselines.

Xiao Liu, Jiaxiang Liu, Boci Peng et al.

Vision Language Models adapt well to downstream tasks but are highly vulnerable to adversarial perturbations that disrupt cross-modal semantic alignment. Existing defenses are largely unidirectional or structural, failing to exploit bidirectional cross-modal complementarity and instance-wise adaptive protection. To overcome the limitations of unidirectional and static defenses in adversarial settings, we propose Closed-Loop Bidirectional Prompting, casting robust adaptation as cross-modal agreement recovery via a dynamic feedback loop on frozen encoders. A Semantic Anchor is introduced as a stable prior to constrain cyclic updates and mitigate perturbation-induced feature corruption. Through anchor-based bootstrapping, textual semantics denoise visual representations, while the refined visuals enable instance-adaptive prompt updating, yielding a rectified and robust consensus. Extensive evaluations across 11 datasets validate state-of-the-art robustness and strong base-to-new generalization, while maintaining a favorable trade-off between computational cost and accuracy.

Yusong Wang, Chaoran Cheng, Shaoning Li et al.

Geometric graph neural networks (GNNs) have emerged as powerful tools for modeling molecular geometry. However, they encounter limitations in effectively capturing long-range interactions in large molecular systems. To address this challenge, we introduce Neural P$^3$M, a versatile enhancer of geometric GNNs to expand the scope of their capabilities by incorporating mesh points alongside atoms and reimaging traditional mathematical operations in a trainable manner. Neural P$^3$M exhibits flexibility across a wide range of molecular systems and demonstrates remarkable accuracy in predicting energies and forces, outperforming on benchmarks such as the MD22 dataset. It also achieves an average improvement of 22% on the OE62 dataset while integrating with various architectures.

Yusong Wang, Shaoning Li, Zun Wang et al.

In the technical report, we provide our solution for OGB-LSC 2022 Graph Regression Task. The target of this task is to predict the quantum chemical property, HOMO-LUMO gap for a given molecule on PCQM4Mv2 dataset. In the competition, we designed two kinds of models: Transformer-M-ViSNet which is an geometry-enhanced graph neural network for fully connected molecular graphs and Pretrained-3D-ViSNet which is a pretrained ViSNet by distilling geomeotric information from optimized structures. With an ensemble of 22 models, ViSNet Team achieved the MAE of 0.0723 eV on the test-challenge set, dramatically reducing the error by 39.75% compared with the best method in the last year competition.

Yusong Wang, Keyu Mao, Takao Obi et al.

Emotion Recognition in Conversation is a core component of affective computing, while current resources of sign language emotion datasets primarily focus on isolated sentences and lack conversational context. Models trained exclusively on these isolated utterances demonstrate degraded performance in real world scenarios because they cannot utilize historical dialogue flow. To address this structural limitation, we introduce the ERC task to sign language video analysis and propose the eJSL Dialog dataset. Constructed using the scripts from the STUDIES corpus, the dataset contains 1,920 video samples organized into 480 unique dialogues. We conduct systematic benchmarking on this dataset using models ranging from isolated visual networks to multimodal conversational architectures. The results reveal a domain gap when applying generic multimodal conversational emotion recognition models to sign language. These findings demonstrate the explicit need for context aware visual extractors specific to sign language and indicate that expanding the scale of conversational datasets to support large scale pre-training is a necessary next step for future research.

Dongyuan Li, Yusong Wang, Kotaro Funakoshi et al.

Speech emotion recognition (SER) has drawn increasing attention for its applications in human-machine interaction. However, existing SER methods ignore the information gap between the pre-training speech recognition task and the downstream SER task, leading to sub-optimal performance. Moreover, they require much time to fine-tune on each specific speech dataset, restricting their effectiveness in real-world scenes with large-scale noisy data. To address these issues, we propose an active learning (AL) based Fine-Tuning framework for SER that leverages task adaptation pre-training (TAPT) and AL methods to enhance performance and efficiency. Specifically, we first use TAPT to minimize the information gap between the pre-training and the downstream task. Then, AL methods are used to iteratively select a subset of the most informative and diverse samples for fine-tuning, reducing time consumption. Experiments demonstrate that using only 20\%pt. samples improves 8.45\%pt. accuracy and reduces 79\%pt. time consumption.

Yang Li, Jiaxiang Liu, Yusong Wang et al.

Language-model-based agents operating over extended interaction horizons face persistent challenges in preserving temporally grounded information and maintaining behavioral consistency across sessions, a failure mode we term soul erosion. We present BMAM (Brain-inspired Multi-Agent Memory), a general-purpose memory architecture that models agent memory as a set of functionally specialized subsystems rather than a single unstructured store. Inspired by cognitive memory systems, BMAM decomposes memory into episodic, semantic, salience-aware, and control-oriented components that operate at complementary time scales. To support long-horizon reasoning, BMAM organizes episodic memories along explicit timelines and retrieves evidence by fusing multiple complementary signals. Experiments on the LoCoMo benchmark show that BMAM achieves 78.45 percent accuracy under the standard long-horizon evaluation setting, and ablation analyses confirm that the hippocampus-inspired episodic memory subsystem plays a critical role in temporal reasoning.

Dongyuan Li, Ying Zhang, Yusong Wang et al.

Speech emotion recognition (SER) has garnered increasing attention due to its wide range of applications in various fields, including human-machine interaction, virtual assistants, and mental health assistance. However, existing SER methods often overlook the information gap between the pre-training speech recognition task and the downstream SER task, resulting in sub-optimal performance. Moreover, current methods require much time for fine-tuning on each specific speech dataset, such as IEMOCAP, which limits their effectiveness in real-world scenarios with large-scale noisy data. To address these issues, we propose an active learning (AL)-based fine-tuning framework for SER, called \textsc{After}, that leverages task adaptation pre-training (TAPT) and AL methods to enhance performance and efficiency. Specifically, we first use TAPT to minimize the information gap between the pre-training speech recognition task and the downstream speech emotion recognition task. Then, AL methods are employed to iteratively select a subset of the most informative and diverse samples for fine-tuning, thereby reducing time consumption. Experiments demonstrate that our proposed method \textsc{After}, using only 20\% of samples, improves accuracy by 8.45\% and reduces time consumption by 79\%. The additional extension of \textsc{After} and ablation studies further confirm its effectiveness and applicability to various real-world scenarios. Our source code is available on Github for reproducibility. (https://github.com/Clearloveyuan/AFTER).

Yusong Wang, Chuang Yang, Jiawei Wang et al.

Human mobility generation aims to synthesize plausible trajectory data, which is widely used in urban system research. While Large Language Model-based methods excel at generating routine trajectories, they struggle to capture deviated mobility during large-scale societal events. This limitation stems from two critical gaps: (1) the absence of event-annotated mobility datasets for design and evaluation, and (2) the inability of current frameworks to reconcile competitions between users' habitual patterns and event-imposed constraints when making trajectory decisions. This work addresses these gaps with a twofold contribution. First, we construct the first event-annotated mobility dataset covering three major events: Typhoon Hagibis, COVID-19, and the Tokyo 2021 Olympics. Second, we propose ELLMob, a self-aligned LLM framework that first extracts competing rationales between habitual patterns and event constraints, based on Fuzzy-Trace Theory, and then iteratively aligns them to generate trajectories that are both habitually grounded and event-responsive. Extensive experiments show that ELLMob wins state-of-the-art baselines across all events, demonstrating its effectiveness. Our codes and datasets are available at https://github.com/deepkashiwa20/ELLMob.

Yusong Wang, Jialun Shen, Zhihao Wu et al.

Graph Neural Networks (GNNs) have been widely adopted for Protein Representation Learning (PRL), as residue interaction networks can be naturally represented as graphs. Current GNN-based PRL methods typically rely on single-perspective graph construction strategies, which capture partial properties of residue interactions, resulting in incomplete protein representations. To address this limitation, we propose MMPG, a framework that constructs protein graphs from multiple perspectives and adaptively fuses them via Mixture of Experts (MoE) for PRL. MMPG constructs graphs from physical, chemical, and geometric perspectives to characterize different properties of residue interactions. To capture both perspective-specific features and their synergies, we develop an MoE module, which dynamically routes perspectives to specialized experts, where experts learn intrinsic features and cross-perspective interactions. We quantitatively verify that MoE automatically specializes experts in modeling distinct levels of interaction from individual representations, to pairwise inter-perspective synergies, and ultimately to a global consensus across all perspectives. Through integrating this multi-level information, MMPG produces superior protein representations and achieves advanced performance on four different downstream protein tasks.

Shaoning Li, Le Zhuo, Yusong Wang et al.

Developing effective representations of protein structures is essential for advancing protein science, particularly for protein generative modeling. Current approaches often grapple with the complexities of the SE(3) manifold, rely on discrete tokenization, or the need for multiple training objectives, all of which can hinder the model optimization and generalization. We introduce ProteinAE, a novel and streamlined protein diffusion autoencoder designed to overcome these challenges by directly mapping protein backbone coordinates from E(3) into a continuous, compact latent space. ProteinAE employs a non-equivariant Diffusion Transformer with a bottleneck design for efficient compression and is trained end-to-end with a single flow matching objective, substantially simplifying the optimization pipeline. We demonstrate that ProteinAE achieves state-of-the-art reconstruction quality, outperforming existing autoencoders. The resulting latent space serves as a powerful foundation for a latent diffusion model that bypasses the need for explicit equivariance. This enables efficient, high-quality structure generation that is competitive with leading structure-based approaches and significantly outperforms prior latent-based methods. Code is available at https://github.com/OnlyLoveKFC/ProteinAE_v1.

Yicheng Xu, Yuxin Chen, Jiahao Nie et al.

Continual learning (CL) with Vision-Language Models (VLMs) has overcome the constraints of traditional CL, which only focuses on previously encountered classes. During the CL of VLMs, we need not only to prevent the catastrophic forgetting on incrementally learned knowledge but also to preserve the zero-shot ability of VLMs. However, existing methods require additional reference datasets to maintain such zero-shot ability and rely on domain-identity hints to classify images across different domains. In this study, we propose Regression-based Analytic Incremental Learning (RAIL), which utilizes a recursive ridge regression-based adapter to learn from a sequence of domains in a non-forgetting manner and decouple the cross-domain correlations by projecting features to a higher-dimensional space. Cooperating with a training-free fusion module, RAIL absolutely preserves the VLM's zero-shot ability on unseen domains without any reference data. Additionally, we introduce Cross-domain Task-Agnostic Incremental Learning (X-TAIL) setting. In this setting, a CL learner is required to incrementally learn from multiple domains and classify test images from both seen and unseen domains without any domain-identity hint. We theoretically prove RAIL's absolute memorization on incrementally learned domains. Experiment results affirm RAIL's state-of-the-art performance in both X-TAIL and existing Multi-domain Task-Incremental Learning settings. The code is released at https://github.com/linghan1997/Regression-based-Analytic-Incremental-Learning.

Jinhua Zhu, Yingce Xia, Chang Liu et al.

Molecular conformation generation aims to generate three-dimensional coordinates of all the atoms in a molecule and is an important task in bioinformatics and pharmacology. Previous methods usually first predict the interatomic distances, the gradients of interatomic distances or the local structures (e.g., torsion angles) of a molecule, and then reconstruct its 3D conformation. How to directly generate the conformation without the above intermediate values is not fully explored. In this work, we propose a method that directly predicts the coordinates of atoms: (1) the loss function is invariant to roto-translation of coordinates and permutation of symmetric atoms; (2) the newly proposed model adaptively aggregates the bond and atom information and iteratively refines the coordinates of the generated conformation. Our method achieves the best results on GEOM-QM9 and GEOM-Drugs datasets. Further analysis shows that our generated conformations have closer properties (e.g., HOMO-LUMO gap) with the groundtruth conformations. In addition, our method improves molecular docking by providing better initial conformations. All the results demonstrate the effectiveness of our method and the great potential of the direct approach. The code is released at https://github.com/DirectMolecularConfGen/DMCG

Zheyuan Gu, Minghao Shao, Zhen Wang et al.

While spatiotemporal deepfake detectors achieve high AUC, our experiments reveal their susceptibility to evasion attacks. These models tend to overfit on fragile temporal spectrum cues, rather than learning robust semantic causality. To mitigate this vulnerability, we propose SpInShield, a temporal spectral-invariant defense framework explicitly designed to decouple semantic motion from manipulatable spectral artifacts. We propose a learnable spectral adversary that dynamically synthesizes severe spectral deformations, simulating extreme attack scenarios. By employing a shortcut suppression optimization strategy, SpInShield compels the encoder to extract reliable forensic cues while purging unstable spectral statistics from the latent space. Experiments show that SpInShield obtains competitive performance on widely used datasets and outperforms the strongest baseline by 21.30 percentage points in AUC under simulated amplitude spectral attacks.

Zheyuan Gu, Qingsong Zhao, Yusong Wang et al.

Current Vision-Language Models (VLMs) for deepfake detection excel at identifying spatial artifacts but overlook a critical dimension: temporal inconsistencies in video forgeries. Adapting VLMs to reason about these dynamic cues remains a distinct challenge. To bridge this gap, we propose Forensic Answer-Questioning (FAQ), a large-scale benchmark that formulates temporal deepfake analysis as a multiple-choice task. FAQ introduces a three-level hierarchy to progressively evaluate and equip VLMs with forensic capabilities: (1) Facial Perception, testing the ability to identify static visual artifacts; (2) Temporal Deepfake Grounding, requiring the localization of dynamic forgery artifacts across frames; and (3) Forensic Reasoning, challenging models to synthesize evidence for final authenticity verdicts. We evaluate a range of VLMs on FAQ and generate a corresponding instruction-tuning set, FAQ-IT. Extensive experiments show that models fine-tuned on FAQ-IT achieve advanced performance on both in-domain and cross-dataset detection benchmarks. Ablation studies further validate the impact of our key design choices, confirming that FAQ is the driving force behind the temporal reasoning capabilities of these VLMs.

Yixian Xu, Yusong Wang, Shengjie Luo et al.

Diffusion-based generative models have reformed generative AI, and have enabled new capabilities in the science domain, for example, generating 3D structures of molecules. Due to the intrinsic problem structure of certain tasks, there is often a symmetry in the system, which identifies objects that can be converted by a group action as equivalent, hence the target distribution is essentially defined on the quotient space with respect to the group. In this work, we establish a formal framework for diffusion modeling on a general quotient space, and apply it to molecular structure generation which follows the special Euclidean group $\text{SE}(3)$ symmetry. The framework reduces the necessity of learning the component corresponding to the group action, hence simplifies learning difficulty over conventional group-equivariant diffusion models, and the sampler guarantees recovering the target distribution, while heuristic alignment strategies lack proper samplers. The arguments are empirically validated on structure generation for small molecules and proteins, indicating that the principled quotient-space diffusion model provides a new framework that outperforms previous symmetry treatments.

Shaoning Li, Yusong Wang, Mingyu Li et al.

Molecular dynamics (MD) is a crucial technique for simulating biological systems, enabling the exploration of their dynamic nature and fostering an understanding of their functions and properties. To address exploration inefficiency, emerging enhanced sampling approaches like coarse-graining (CG) and generative models have been employed. In this work, we propose a \underline{Frame-to-Frame} generative model with guided \underline{Flow}-matching (F$3$low) for enhanced sampling, which (a) extends the domain of CG modeling to the SE(3) Riemannian manifold; (b) retreating CGMD simulations as autoregressively sampling guided by the former frame via flow-matching models; (c) targets the protein backbone, offering improved insights into secondary structure formation and intricate folding pathways. Compared to previous methods, F$3$low allows for broader exploration of conformational space. The ability to rapidly generate diverse conformations via force-free generative paradigm on SE(3) paves the way toward efficient enhanced sampling methods.

Yihan Hou, Xingchen Zeng, Yusong Wang et al.

Existing approaches for color-concept association typically rely on query-based image referencing, and color extraction from image references. However, these approaches are effective only for common concepts, and are vulnerable to unstable image referencing and varying image conditions. Our formative study with designers underscores the need for primary-accent color compositions and context-dependent colors (e.g., 'clear' vs. 'polluted' sky) in design. In response, we introduce a generative approach for mining semantically resonant colors leveraging images generated by text-to-image models. Our insight is that contemporary text-to-image models can resemble visual patterns from large-scale real-world data. The framework comprises three stages: concept instancing produces generative samples using diffusion models, text-guided image segmentation identifies concept-relevant regions within the image, and color association extracts primarily accompanied by accent colors. Quantitative comparisons with expert designs validate our approach's effectiveness, and we demonstrate the applicability through cases in various design scenarios and a gallery.

Kaiyuan Gao, Yusong Wang, Haoxiang Guan et al.

The application of language models (LMs) to molecular structure generation using line notations such as SMILES and SELFIES has been well-established in the field of cheminformatics. However, extending these models to generate 3D molecular structures presents significant challenges. Two primary obstacles emerge: (1) the difficulty in designing a 3D line notation that ensures SE(3)-invariant atomic coordinates, and (2) the non-trivial task of tokenizing continuous coordinates for use in LMs, which inherently require discrete inputs. To address these challenges, we propose Mol-StrucTok, a novel method for tokenizing 3D molecular structures. Our approach comprises two key innovations: (1) We design a line notation for 3D molecules by extracting local atomic coordinates in a spherical coordinate system. This notation builds upon existing 2D line notations and remains agnostic to their specific forms, ensuring compatibility with various molecular representation schemes. (2) We employ a Vector Quantized Variational Autoencoder (VQ-VAE) to tokenize these coordinates, treating them as generation descriptors. To further enhance the representation, we incorporate neighborhood bond lengths and bond angles as understanding descriptors. Leveraging this tokenization framework, we train a GPT-2 style model for 3D molecular generation tasks. Results demonstrate strong performance with significantly faster generation speeds and competitive chemical stability compared to previous methods. Further, by integrating our learned discrete representations into Graphormer model for property prediction on QM9 dataset, Mol-StrucTok reveals consistent improvements across various molecular properties, underscoring the versatility and robustness of our approach.

Haodong Pan, Hao Wei, Yusong Wang et al.

Learned image compression (LIC) has recently benefited from Transformer based and state space model (SSM) based architectures. Convolutional neural networks (CNNs) effectively capture local high frequency details, whereas Transformers and SSMs provide strong long range modeling capabilities but may cause structural information loss or ignore frequency characteristics that are crucial for compression. In this work we propose HCFSSNet, a Hybrid Convolution and Frequency State Space Network for LIC. HCFSSNet uses CNNs to extract local high frequency structures and introduces a Vision Frequency State Space (VFSS) block that models long range low frequency information. The VFSS block combines an Omni directional Neighborhood State Space (VONSS) module, which scans features horizontally, vertically and diagonally, with an Adaptive Frequency Modulation Module (AFMM) that applies content adaptive weighting of discrete cosine transform frequency components for more efficient bit allocation. To further reduce redundancy in the entropy model, we integrate AFMM with a Swin Transformer to form a Frequency Swin Transformer Attention Module (FSTAM) for frequency aware side information modeling. Experiments on the Kodak, Tecnick and CLIC Professional Validation datasets show that HCFSSNet achieves competitive rate distortion performance compared with recent SSM based codecs such as MambaIC, while using significantly fewer parameters. On Kodak, Tecnick and CLIC, HCFSSNet reduces BD rate over the VTM anchor by 18.06, 24.56 and 22.44 percent, respectively, providing an efficient and interpretable hybrid architecture for future learned image compression systems.

Chaoran Cheng, Yusong Wang, Yuxin Chen et al.

Consistency models are a class of generative models that enable few-step generation for diffusion and flow matching models. While consistency models have achieved promising results on Euclidean domains like images, their applications to Riemannian manifolds remain challenging due to the curved geometry. In this work, we propose the Riemannian Consistency Model (RCM), which, for the first time, enables few-step consistency modeling while respecting the intrinsic manifold constraint imposed by the Riemannian geometry. Leveraging the covariant derivative and exponential-map-based parameterization, we derive the closed-form solutions for both discrete- and continuous-time training objectives for RCM. We then demonstrate theoretical equivalence between the two variants of RCM: Riemannian consistency distillation (RCD) that relies on a teacher model to approximate the marginal vector field, and Riemannian consistency training (RCT) that utilizes the conditional vector field for training. We further propose a simplified training objective that eliminates the need for the complicated differential calculation. Finally, we provide a unique kinematics perspective for interpreting the RCM objective, offering new theoretical angles. Through extensive experiments, we manifest the superior generative quality of RCM in few-step generation on various non-Euclidean manifolds, including flat-tori, spheres, and the 3D rotation group SO(3).

Haodong Pan, Yusong Wang, Nanning Zheng et al.

Geometric graph neural networks (GNNs) excel at capturing molecular geometry, yet their locality-biased message passing hampers the modeling of long-range interactions. Current solutions have fundamental limitations: extending cutoff radii causes computational costs to scale cubically with distance; physics-inspired kernels (e.g., Coulomb, dispersion) are often system-specific and lack generality; Fourier-space methods require careful tuning of multiple parameters (e.g., mesh size, k-space cutoff) with added computational overhead. We introduce Multi-stage Clustered Global Modeling (MCGM), a lightweight, plug-and-play module that endows geometric GNNs with hierarchical global context through efficient clustering operations. MCGM builds a multi-resolution hierarchy of atomic clusters, distills global information via dynamic hierarchical clustering, and propagates this context back through learned transformations, ultimately reinforcing atomic features via residual connections. Seamlessly integrated into four diverse backbone architectures, MCGM reduces OE62 energy prediction error by an average of 26.2%. On AQM, MCGM achieves state-of-the-art accuracy (17.0 meV for energy, 4.9 meV/Å for forces) while using 20% fewer parameters than Neural P3M. Code will be made available upon acceptance.

Yuheng Ding, Bo Qiang, Yiran Zhou et al.

Natural products, as metabolites from microorganisms, animals, or plants, exhibit diverse biological activities, making them crucial for drug discovery. Nowadays, existing deep learning methods for natural products research primarily rely on supervised learning approaches designed for specific downstream tasks. However, such one-model-for-a-task paradigm often lacks generalizability and leaves significant room for performance improvement. Additionally, existing molecular characterization methods are not well-suited for the unique tasks associated with natural products. To address these limitations, we have pre-trained a foundation model for natural products based on their unique properties. Our approach employs a novel pretraining strategy that is especially tailored to natural products. By incorporating contrastive learning and masked graph learning objectives, we emphasize evolutional information from molecular scaffolds while capturing side-chain information. Our framework achieves state-of-the-art (SOTA) results in various downstream tasks related to natural product mining and drug discovery. We first compare taxonomy classification with synthesized molecule-focused baselines to demonstrate that current models are inadequate for understanding natural synthesis. Furthermore, by diving into a fine-grained analysis at both the gene and microbial levels, NaFM demonstrates the ability to capture evolutionary information. Eventually, our method is experimented with virtual screening, illustrating informative natural product representations that can lead to more effective identification of potential drug candidates.

Siyuan Liu, Yusong Wang, Tong Wang et al.

The identification of active binding drugs for target proteins (termed as drug-target interaction prediction) is the key challenge in virtual screening, which plays an essential role in drug discovery. Although recent deep learning-based approaches achieved better performance than molecular docking, existing models often neglect certain aspects of the intermolecular information, hindering the performance of prediction. We recognize this problem and propose a novel approach named Intermolecular Graph Transformer (IGT) that employs a dedicated attention mechanism to model intermolecular information with a three-way Transformer-based architecture. IGT outperforms state-of-the-art approaches by 9.1% and 20.5% over the second best for binding activity and binding pose prediction respectively, and shows superior generalization ability to unseen receptor proteins. Furthermore, IGT exhibits promising drug screening ability against SARS-CoV-2 by identifying 83.1% active drugs that have been validated by wet-lab experiments with near-native predicted binding poses.