MOTIVATION: Structure-based drug design (SBDD) aims to generate ligand molecules that tightly bind to specific protein targets, a critical step in drug discovery. Diffusion models have shown promise for this task, yet existing methods struggle to effectively incorporate protein-ligand interaction priors during generation. Most approaches rely on protein-specific structural priors that remain fixed throughout generation, limiting molecular diversity and failing to capture the dynamic interplay between protein pockets and ligand atoms, which is essential for achieving high binding affinity. RESULTS: We propose DPDiff, a disentangled prior-conditioned diffusion model for protein-specific 3D molecular generation. DPDiff introduces two complementary interaction prior networks that capture geometry-based spatial interactions and sequence-based interactions robust to structural noise. During generation, the model dynamically extracts interaction priors using intermediate diffusion predictions and adaptively fuses them via a time-dependent adapter. A disentangled denoising network balances prior guidance with generative flexibility. Experiments on the CrossDocked2020 dataset demonstrate that DPDiff generates molecules with more realistic 3D structures and state-of-the-art binding affinities, achieving an average Vina Dock score of -8.58 and a high affinity ratio of 69.4%, outperforming existing methods while maintaining favorable drug-likeness and synthetic accessibility. AVAILABILITY AND IMPLEMENTATION: The source code of DPDiff is available at https://github.com/ZerinHwang03/DPDiff.

The objective of video frame interpolation (VFI) methods is to enhance video fluency and visual quality by generating intermediate frames between consecutive original frames based on the source video. Recently, diffusion-based VFI methods have made promising progresses, with generated results performing well in perceptual quality. However, these methods have not fully explored how to effectively leverage external motion priors to enhance the model's ability to estimate motion information between adjacent frames, which is crucial for VFI models to avoid generating blurry results due to the motion ambiguity. In this paper, we propose an Enhanced Motion-Aware latent Diffusion model ( EMADiff ) for video frame interpolation. Specifically, we integrate motion priors into the decoder of vector-quantized enhanced motion-aware GAN to guide the information propagation during RGB interpolated frame reconstruction. Furthermore, we propose enhanced motion-aware noising and de-noising procedures. By reducing the discrepancy in attention to motion priors between the forward and reverse processes, our EMADiff effectively utilizes motion priors, alleviates motion ambiguity, and generates realistic content. Comprehensive experiments on benchmark datasets show EMADiff achieves state-of-the-art performance, surpassing existing approaches and producing visually plausible and content-clear results.

Structure-based drug design (SBDD) aims to generate 3D ligand molecules that bind to specific protein targets. Existing 3D deep generative models including diffusion models have shown great promise for SBDD. However, it is complex to capture the essential protein-ligand interactions exactly in 3D space for molecular generation. To address this problem, we propose a novel framework, namely Binding-Adaptive Diffusion Models (BindDM). In BindDM, we adaptively extract subcomplex, the essential part of binding sites responsible for protein-ligand interactions. Then the selected protein-ligand subcomplex is processed with SE(3)-equivariant neural networks, and transmitted back to each atom of the complex for augmenting the target-aware 3D molecule diffusion generation with binding interaction information. We iterate this hierarchical complex-subcomplex process with cross-hierarchy interaction node for adequately fusing global binding context between the complex and its corresponding subcomplex. Empirical studies on the CrossDocked2020 dataset show BindDM can generate molecules with more realistic 3D structures and higher binding affinities towards the protein targets, with up to -5.92 Avg. Vina Score, while maintaining proper molecular properties. Our code is available at https://github.com/YangLing0818/BindDM

Event Stream Super-Resolution (ESR) aims to address the challenge of insufficient spatial resolution in event streams, which holds great significance for the application of event cameras in complex scenarios. Previous works for ESR often process positive and negative events in a mixed paradigm. This paradigm limits their ability to effectively model the unique characteristics of each event and mutually refine each other by considering their correlations. In this paper, we propose a bilateral event mining and complementary network (BMCNet) to fully leverage the potential of each event and capture the shared information to complement each other simultaneously. Specifically, we resort to a two-stream network to accomplish comprehensive mining of each type of events individually. To facilitate the exchange of information between two streams, we propose a bilateral information exchange (BIE) module. This module is layer-wisely embedded between two streams, enabling the effective propagation of hierarchical global information while alleviating the impact of invalid information brought by inherent characteristics of events. The experimental results demonstrate that our approach outperforms the previous state-of-the-art methods in ESR, achieving performance improvements of over 11% on both real and synthetic datasets. Moreover, our method significantly enhances the performance of event-based downstream tasks such as object recognition and video reconstruction. Our code is available at https://github.com/Lqm26/BMCNet-ESR.

Generating 3D ligand molecules that bind to specific protein targets via diffusion models has shown great promise for structure-based drug design. The key idea is to disrupt molecules into noise through a fixed forward process and learn its reverse process to generate molecules from noise in a denoising way. However, existing diffusion models primarily focus on incorporating protein-ligand interaction information solely in the reverse process, and neglect the interactions in the forward process. The inconsistency between forward and reverse processes may impair the binding affinity of generated molecules towards target protein. In this paper, we propose a novel Interaction Prior-guided Diffusion model (IPDiff) for the protein-specific 3D molecular generation by introducing geometric protein-ligand interactions into both diffusion and sampling process. Specifically, we begin by pretraining a protein-ligand interaction prior network (IPNet) by utilizing the binding affinity signals as supervision. Subsequently, we leverage the pretrained prior network to (1) integrate interactions between the target protein and the molecular ligand into the forward process for adapting the molecule diffusion trajectories (prior-shifting), and (2) enhance the binding-aware molecule sampling process (prior-conditioning). Empirical studies on CrossDocked2020 dataset show IPDiff can generate molecules with more realistic 3D structures and state-of-the-art binding affinities towards the protein targets, with up to -6.42 Avg. Vina Score, while maintaining proper molecular properties. https://github.com/YangLing0818/IPDiff

Generating ligand molecules that bind to specific protein targets via generative models holds substantial promise for advancing structure-based drug design. Existing methods generate molecules from scratch without reference or template ligands, which poses challenges in model optimization and may yield suboptimal outcomes. To address this problem, we propose an innovative interaction-based retrieval-augmented diffusion model named IRDiff to facilitate target-aware molecule generation. IRDiff leverages a curated set of ligand references, i.e., those with desired properties such as high binding affinity, to steer the diffusion model towards synthesizing ligands that satisfy design criteria. Specifically, we utilize a protein-molecule interaction network (PMINet), which is pretrained with binding affinity signals to: (i) retrieve target-aware ligand molecules with high binding affinity to serve as references, and (ii) incorporate essential protein-ligand binding structures for steering molecular diffusion generation with two effective augmentation mechanisms, i.e., retrieval augmentation and self augmentation. Empirical studies on CrossDocked2020 dataset show IRDiff can generate molecules with more realistic 3D structures and achieve state-of-the-art binding affinities towards the protein targets, while maintaining proper molecular properties. The codes and models are available at https://github.com/YangLing0818/IRDiff

With the advancement of AIGC, video frame interpolation (VFI) has become a crucial component in existing video generation frameworks, attracting widespread research interest. For the VFI task, the motion estimation between neighboring frames plays a crucial role in avoiding motion ambiguity. However, existing VFI methods always struggle to accurately predict the motion information between consecutive frames, and this imprecise estimation leads to blurred and visually incoherent interpolated frames. In this paper, we propose a novel diffusion framework, Motion-Aware latent Diffusion models (MADiff), which is specifically designed for the VFI task. By incorporating motion priors between the conditional neighboring frames with the target interpolated frame predicted throughout the diffusion sampling procedure, MADiff progressively refines the intermediate outcomes, culminating in generating both visually smooth and realistic results. Extensive experiments conducted on benchmark datasets demonstrate that our method achieves state-of-the-art performance significantly outperforming existing approaches, especially under challenging scenarios involving dynamic textures with complex motion.

Graph generation is a fundamental task in machine learning with broad impacts on numerous real-world applications such as biomedical discovery and social science. Most recently, generative models, especially diffusion models (DMs), have shown great promise in synthesizing realistic graphs. However, existing DMs methods typically conduct diffusion processes directly in complex graph space (i.e., node feature, adjacency matrix, or both), resulting in high modeling complexity and poor multimodal distribution coverage. In this paper, we propose Graphusion, a novel and unified latent-based graph generative framework to address the problems. Specifically, Graphusion is composed of a variational graph autoencoder mapping raw graphs with high-dimensional discrete space to low-dimensional topology-injected latent space, and latent DMs running there, producing a smoother, faster, and more expressive graph generation procedure. Thanks to the latest space modeling, we further develop principled latent self-guidance to sufficiently cover the whole semantical distribution of the unlabeled graph set. Experiments show that our Graphusion framework can consistently outperform previous graph generation baselines on both generic and molecular graph datasets, demonstrating the generality and extensibility along with further analytical justifications.

Out-of-distribution (OOD) graph generalization are critical for many real-world applications. Existing methods neglect to discard spurious or noisy features of inputs, which are irrelevant to the label. Besides, they mainly conduct instance-level class-invariant graph learning and fail to utilize the structural class relationships between graph instances. In this work, we endeavor to address these issues in a unified framework, dubbedIndividual andStructuralGraphInformationBottlenecks (IS-GIB). To remove class spurious feature caused by distribution shifts, we propose Individual Graph Information Bottleneck (I-GIB) which discards irrelevant information by minimizing the mutual information between the input graph and its embeddings. To leverage the structural intra- and inter-domain correlations, we propose Structural Graph Information Bottleneck (S-GIB). Specifically for a batch of graphs with multiple domains, S-GIB first computes the pair-wise input-input, embedding-embedding, and label-label correlations. Then it minimizes the mutual information between input graph and embedding pairs while maximizing the mutual information between embedding and label pairs. The critical insight of S-GIB is to simultaneously discard spurious features and learn invariant features from a high-order perspective by maintaining class relationships under multiple distributional shifts. Notably, we unify the proposed I-GIB and S-GIB to form our complementary framework IS-GIB. Extensive experiments conducted on both node- and graph-level tasks consistently demonstrate the superior generalization ability of IS-GIB. The code is available athttps://github.com/YangLing0818/GraphOOD.

Diffusion models are a new class of generative models, and have dramatically promoted image generation with unprecedented quality and diversity. Existing diffusion models mainly try to reconstruct input image from a corrupted one with a pixel-wise or feature-wise constraint along spatial axes. However, such point-based reconstruction may fail to make each predicted pixel/feature fully preserve its neighborhood context, impairing diffusion-based image synthesis. As a powerful source of automatic supervisory signal, context has been well studied for learning representations. Inspired by this, we for the first time propose ConPreDiff to improve diffusion-based image synthesis with context prediction. We explicitly reinforce each point to predict its neighborhood context (i.e., multi-stride pixels/features) with a context decoder at the end of diffusion denoising blocks in training stage, and remove the decoder for inference. In this way, each point can better reconstruct itself by preserving its semantic connections with neighborhood context. This new paradigm of ConPreDiff can generalize to arbitrary discrete and continuous diffusion backbones without introducing extra parameters in sampling procedure. Extensive experiments are conducted on unconditional image generation, text-to-image generation and image inpainting tasks. Our ConPreDiff consistently outperforms previous methods and achieves new SOTA text-to-image generation results on MS-COCO, with a zero-shot FID score of 6.21.

Recent attention-based image inpainting methods have made inspiring progress by propagating distant contextual information into holes. However, they tend to generate blurry contents since the propagation process is always misled by preliminarily-recovered holes features which are not well-inferred. To handle this problem, we propose a novel semantic-aware context aggregation module (SACA) that aggregates distant contextual information from a semantic perspective by exploiting the internal semantic similarity of the input feature map. Compared with existing attention mechanisms that model the relation of all pixel-pairs, SACA can suppress the impact of misleading holes features in context aggregation and significantly reduce computation burden by learning the relation between pixels and semantics. Also, we apply SACA to both high-level and low-level feature maps in our model for generating both semantically and visually plausible results. Extensive experiments on Outdoor Scenes, CelebA and Paris StreetView datasets validate the superiority of our method compared with existing methods.

Existing image inpainting methods have shown their potential in filling corrupted regions with plausible contents. However, these methods tend to produce results with distorted structures or unnatural textures since they neglect the difference between structures and textures in images and jointly process these two different types of information. To solve this problem, we propose a bi-encoder network (BE-Net) that seeks to handle structure and texture information separately, and fuse them to reconstruct completed images. Specifically, BE-Net first uses two parallel encoders to infer structure and texture features of the input images respectively. Then a structure-texture consistency module (STCM) is designed to weaken artifacts and enhance visual coherency of the output images by keeping the texture features consistent with the structure features. Finally, the structure features and the texture features are fused at each level of the decoder to recover images with reasonable structures and realistic textures. Extensive experiments on Paris StreetView and CelebA datasets show the proposed approach is effective in generating realistic and visually plausible results and outperforms several state-of-the-art methods.