Fang Wu, Hongbin Lin, Bingchen Duan, Yuchen Wang, Li Erran Li, Yanjie Huang, Mingxuan Cao, Yijun Ma 等 27 位作者
Protein-protein interactions underpin nearly all biological processes. Yet, designing proteins with desired interactions remains challenging due to the structural complexity governing molecular recognition. This study views protein design as a search optimization problem over a combinatorial sequence space under expensive structural evaluation. Toward this goal, we introduce a novel tree-based search framework, ProteoCraft, that employs approximate structural gradients from diffusion-based structure predictors as effective proposal policies to specify where the search should explore. Complete no-gradient inference of folding models separately assigns values to the resulting sequences, determining what is good. ProteoCraft allocates this verification budget through a coarse-to-fine paradigm: multi-site edits first explore distinct sequence basins, then verified promising states undergo strict single-site refinement. Across fourteen de novo binder-design settings spanning eight target proteins, five immune-relevant TCR-facing targets, and four localized CDR redesign tasks, ProteoCraft improves design quality and high-confidence yield. These improvements persist under independent AF2-IG and Rosetta-based interface evaluation. Prospective experimental validation further yielded an 82.9% binding hit rate for PD-L1 miniproteins, with a best measured KD of 0.879 nM, and confirmed binding of designed IFNAR2 VHH. Our code is available at https://github.com/smiles724/ProteoCraft_v1.
We present Xiaomi Auto World Model 2.0, a unified streaming causal world model for Physical AI. It models and generates causal physical evolution in the real world, and unifies heterogeneous conditioning inputs for view-consistent generation. The architecture integrates View-Temporal Attention (VTA) to capture cross-view spatial dependencies and temporal dynamics, together with Multi-view Rotary Position Encoding (RoPE) to encode positional relationships across views and time. WorldRec 2.0 reconstructs static and dynamic 3D Gaussians from multi-view, multi-temporal observations in a single forward pass and uses their renderings as explicit scene context to preserve geometry and appearance during long-horizon generation. Conditioning inputs are fused through VAE latent concatenation in a shared representation space. We incorporate Gated Linear Attention (GLA) into the temporal layers of VTA for efficient streaming inference, reducing computation and KV-cache memory during multi-view rollouts. A physical-interaction data pipeline covers diverse interactions and long-tailed events. From Pre-train onward, these data are combined with large-scale videos and heterogeneous visual modalities to learn visual, geometric, and dynamic priors. During Mid-train, training across diverse view configurations further improves the model's ability to capture how actions and object states shape subsequent scene evolution. After distillation-based Post-train, we apply the model to closed-loop simulation, closed-loop training, and World Action Model (WAM) applications. These applications generate physically consistent future states and support world-state prediction, policy learning, and action generation for Physical AI.
Xuanfa Jin, Xinyu Cui, Zhijian Ma, Xue Yan, Jian Zhao, Haifeng Zhang, Jun Wang
Epistemic game theory explains an agent's strategic behavior via the beliefs it holds about others and how these beliefs are updated as the interactions unfold. Modern LLM-based agents, however, often lack an explicit mechanism for learning and updating such beliefs to guide decisions under incomplete information. To bridge this gap, we propose EpiAgent, a framework that equips LLM-based agents with an explicit, learnable epistemic layer, which maintains beliefs over others' private information and combines these beliefs with the agent's available information into an epistemic state for action selection. Concretely, the agent's policy is decomposed into two coupled stages: Epistemic Update, which updates these beliefs from interaction histories, and Action Planning, which selects actions conditioned on the updated epistemic state. By formulating their dependency as a bi-level optimization problem, we introduce Epistemic Self-Play, an algorithm that alternately optimizes the two stages through self-play, utilizing an intrinsic prediction reward to evaluate how well inferred beliefs predict subsequent observations. Empirical results across both mixed and competitive scenarios show that EpiAgent consistently outperforms prompting-based and RL-based baselines. Further analyses reveal the benefits of dedicated epistemic training, improvements in belief inference accuracy, and the contribution of learned beliefs to action planning. These results demonstrate the value of an explicit, learnable epistemic layer for effective multi-agent interactions.
Zhimu Zhou, Yanpeng Zhao, Qiuyu Liao, Bo Zhao, Xiaojian Ma
Visual planning represents a crucial facet of human intelligence, especially in tasks that require complex spatial reasoning and navigation. Yet, in machine learning, this inherently visual problem is often tackled through a verbal-centric lens. While recent research demonstrates the promise of fully visual approaches, they suffer from significant computational inefficiency due to the step-by-step planning-by-generation paradigm. In this work, we present EAR, an editing-as-reasoning paradigm that reformulates visual planning as a single-step image transformation. To isolate intrinsic reasoning from visual recognition, we employ abstract puzzles as probing tasks and introduce AMAZE, a procedurally generated dataset that features the classical Maze and Queen problems, covering distinct, complementary forms of visual planning. The abstract nature of AMAZE also facilitates automatic evaluation of autoregressive and diffusion-based models in terms of both pixel-wise fidelity and logical validity. We assess leading proprietary and open-source editing models. The results show that they all struggle in the zero-shot setting, finetuning on basic scales enables remarkable generalization to larger in-domain scales and out-of-domain scales and geometries. However, our best model that runs on high-end hardware fails to match the zero-shot efficiency of human solvers, highlighting a persistent gap in neural visual reasoning.
Hao Cui, Zahra Shamsi, Gowoon Cheon, Xuejian Ma, Shutong Li, Maria Tikhanovskaya, Peter Norgaard, Nayantara Mudur 等 34 位作者
Scientific problem-solving involves synthesizing information while applying expert knowledge. We introduce CURIE, a scientific long-Context Understanding,Reasoning and Information Extraction benchmark to measure the potential of Large Language Models (LLMs) in scientific problem-solving and assisting scientists in realistic workflows. This benchmark introduces ten challenging tasks with a total of 580 problems and solution pairs curated by experts in six disciplines - materials science, condensed matter physics, quantum computing, geospatial analysis, biodiversity, and proteins - covering both experimental and theoretical work-flows in science. We evaluate a range of closed and open LLMs on tasks in CURIE which requires domain expertise, comprehension of long in-context information,and multi-step reasoning. While Gemini Flash 2.0 and Claude-3 show consistent high comprehension across domains, the popular GPT-4o and command-R+ fail dramatically on protein sequencing tasks. With the best performance at 32% there is much room for improvement for all models. We hope that insights gained from CURIE can guide the future development of LLMs in sciences. Evaluation code and data are in https://github.com/google/curie