Designing protein binders targeting specific sites, which requires to generate realistic and functional interaction patterns, is a fundamental challenge in drug discovery. Current structure-based generative models are limited in generating nterfaces with sufficient rationality and interpretability. In this paper, we propose Retrieval-Augmented Diffusion for Aligned interface(RADiAnce), a new framework that leverages known interfaces to guide the design of novel binders. By unifying retrieval and generation in a shared contrastive latent space, our model efficiently identifies relevant interfaces for a given binding site and seamlessly integrates them through a conditional latent diffusion generator, enabling crossdomain interface transfer. Extensive exeriments show that RADiAnce significantly outperforms baseline models across multiple metrics, including binding affinity and recovery of geometries and interactions. Additional experimental results validate cross-domain generalization, demonstrating that retrieving interfaces from diverse domains, such as peptides, antibodies, and protein fragments, enhances the generation performance of binders for other domains. Our work establishes a new paradigm for protein binder design that successfully bridges retrieval-based knowledge and generative AI, opening new possibilities for drug discovery.

Generative models for structure-based drug design are often limited to a specific modality, restricting their broader applicability. To address this challenge, we introduce FuncBind, a framework based on computer vision to generate targetconditioned, all-atom molecules across atomic systems. FuncBind uses neural fields to represent molecules as continuous atomic densities and employs scorebased generative models with modern architectures adapted from the computer vision literature. This modality-agnostic representation allows a single unified model to be trained on diverse atomic systems, from small to large molecules, and handle variable atom/residue counts, including non-canonical amino acids. FuncBind achieves competitive in silico performance in generating small molecules, macrocyclic peptides, and antibody complementarity-determining region loops, conditioned on target structures. FuncBind also generated in vitro novel antibody binders via de novo redesign of the complementarity-determining region H3 loop of two chosen co-crystal structures. As a final contribution, we introduce a new dataset and benchmark for structure-conditioned macrocyclic peptide generation*.

Designing protein binders targeting specific sites, which requires to generate realistic and functional interaction patterns, is a fundamental challenge in drug discovery. Current structure-based generative models are limited in generating nterfaces with sufficient rationality and interpretability.

We introduce AbDiffuser, an equivariant and physics-informed diffusion model for the joint generation of antibody 3D structures and sequences. AbDiffuser is built on top of a new representation of protein structure, relies on a novel architecture for aligned proteins, and utilizes strong diffusion priors to improve the denoising process. Our approach improves protein diffusion by taking advantage of domain knowledge and physics-based constraints; handles sequence-length changes; and reduces memory complexity by an order of magnitude, enabling backbone and side chain generation.

Visual concept composition, which aims to integrate different elements from images and videos into a single, coherent visual output, still falls short in accurately extracting complex concepts from visual inputs and flexibly combining concepts from both images and videos. We introduce Bind & Compose, a one-shot method that enables flexible visual concept composition by binding visual concepts with corresponding prompt tokens and composing the target prompt with bound tokens from various sources. It adopts a hierarchical binder structure for cross-attention conditioning in Diffusion Transformers to encode visual concepts into corresponding prompt tokens for accurate decomposition of complex visual concepts. To improve concept-token binding accuracy, we design a Diversify-and-Absorb Mechanism that uses an extra absorbent token to eliminate the impact of concept-irrelevant details when training with diversified prompts. To enhance the compatibility between image and video concepts, we present a Temporal Disentanglement Strategy that decouples the training process of video concepts into two stages with a dual-branch binder structure for temporal modeling. Evaluations demonstrate that our method achieves superior concept consistency, prompt fidelity, and motion quality over existing approaches, opening up new possibilities for visual creativity.

Open-vocabulary mobile manipulation (OVMM) requires robots to follow language instructions, navigate, and manipulate while updating their world representation under dynamic environmental changes. However, most prior approaches update their world representation only at discrete update points such as navigation targets, waypoints, or the end of an action step, leaving robots blind between updates and causing cascading failures: overlooked objects, late error detection, and delayed replanning. To address this limitation, we propose BINDER (Bridging INstant and DEliberative Reasoning), a dual process framework that decouples strategic planning from continuous environment monitoring. Specifically, BINDER integrates a Deliberative Response Module (DRM, a multimodal LLM for task planning) with an Instant Response Module (IRM, a VideoLLM for continuous monitoring). The two modules play complementary roles: the DRM performs strategic planning with structured 3D scene updates and guides what the IRM attends to, while the IRM analyzes video streams to update memory, correct ongoing actions, and trigger replanning when necessary. Through this bidirectional coordination, the modules address the trade off between maintaining awareness and avoiding costly updates, enabling robust adaptation under dynamic conditions. Evaluated in three real world environments with dynamic object placement, BINDER achieves substantially higher success and efficiency than SoTA baselines, demonstrating its effectiveness for real world deployment.

Generative models for structure-based drug design are often limited to a specific modality, restricting their broader applicability. To address this challenge, we introduce FuncBind, a framework based on computer vision to generate target-conditioned, all-atom molecules across atomic systems. FuncBind uses neural fields to represent molecules as continuous atomic densities and employs score-based generative models with modern architectures adapted from the computer vision literature. This modality-agnostic representation allows a single unified model to be trained on diverse atomic systems, from small to large molecules, and handle variable atom/residue counts, including non-canonical amino acids. FuncBind achieves competitive in silico performance in generating small molecules, macrocyclic peptides, and antibody complementarity-determining region loops, conditioned on target structures. FuncBind also generated in vitro novel antibody binders via de novo redesign of the complementarity-determining region H3 loop of two chosen co-crystal structures. As a final contribution, we introduce a new dataset and benchmark for structure-conditioned macrocyclic peptide generation. The code is available at https://github.com/prescient-design/funcbind.

Designing protein-binding proteins with high affinity is critical in biomedical research and biotechnology. Despite recent advancements targeting specific proteins, the ability to create high-affinity binders for arbitrary protein targets on demand, without extensive rounds of wet-lab testing, remains a significant challenge. Here, we introduce PPDiff, a diffusion model to jointly design the sequence and structure of binders for arbitrary protein targets in a non-autoregressive manner. PPDiffbuilds upon our developed Sequence Structure Interleaving Network with Causal attention layers (SSINC), which integrates interleaved self-attention layers to capture global amino acid correlations, k-nearest neighbor (kNN) equivariant graph layers to model local interactions in three-dimensional (3D) space, and causal attention layers to simplify the intricate interdependencies within the protein sequence. To assess PPDiff, we curate PPBench, a general protein-protein complex dataset comprising 706,360 complexes from the Protein Data Bank (PDB). The model is pretrained on PPBenchand finetuned on two real-world applications: target-protein mini-binder complex design and antigen-antibody complex design. PPDiffconsistently surpasses baseline methods, achieving success rates of 50.00%, 23.16%, and 16.89% for the pretraining task and the two downstream applications, respectively. The code, data and models are available at https://github.com/JocelynSong/PPDiff.

Designing protein binders targeting specific sites, which requires to generate realistic and functional interaction patterns, is a fundamental challenge in drug discovery. Current structure-based generative models are limited in generating nterfaces with sufficient rationality and interpretability. In this paper, we propose Retrieval-Augmented Diffusion for Aligned interface (RADiAnce), a new framework that leverages known interfaces to guide the design of novel binders. By unifying retrieval and generation in a shared contrastive latent space, our model efficiently identifies relevant interfaces for a given binding site and seamlessly integrates them through a conditional latent diffusion generator, enabling cross-domain interface transfer. Extensive exeriments show that RADiAnce significantly outperforms baseline models across multiple metrics, including binding affinity and recovery of geometries and interactions. Additional experimental results validate cross-domain generalization, demonstrating that retrieving interfaces from diverse domains, such as peptides, antibodies, and protein fragments, enhances the generation performance of binders for other domains. Our work establishes a new paradigm for protein binder design that successfully bridges retrieval-based knowledge and generative AI, opening new possibilities for drug discovery.