Quanquan Gu

Yanru Qu, Cheng-Yen Hsieh, Zaixiang Zheng et al.

We present protein autoregressive modeling (PAR), the first multi-scale autoregressive framework for protein backbone generation via coarse-to-fine next-scale prediction. Using the hierarchical nature of proteins, PAR generates structures that mimic sculpting a statue, forming a coarse topology and refining structural details over scales. To achieve this, PAR consists of three key components: (i) multi-scale downsampling operations that represent protein structures across multiple scales during training; (ii) an autoregressive transformer that encodes multi-scale information and produces conditional embeddings to guide structure generation; (iii) a flow-based backbone decoder that generates backbone atoms conditioned on these embeddings. Moreover, autoregressive models suffer from exposure bias, caused by the training and the generation procedure mismatch, and substantially degrades structure generation quality. We effectively alleviate this issue by adopting noisy context learning and scheduled sampling, enabling robust backbone generation. Notably, PAR exhibits strong zero-shot generalization, supporting flexible human-prompted conditional generation and motif scaffolding without requiring fine-tuning. On the unconditional generation benchmark, PAR effectively learns protein distributions and produces backbones of high design quality, and exhibits favorable scaling behavior. Together, these properties establish PAR as a promising framework for protein structure generation.

Kaixuan Ji, Qingyue Zhao, Heyang Zhao et al.

Recent studies have shown that reinforcement learning with KL-regularized objectives can enjoy faster rates of convergence or logarithmic regret, in contrast to the classical $\sqrt{T}$-type regret in the unregularized setting. However, the statistical efficiency of online learning with respect to KL-regularized objectives remains far from completely characterized, even when specialized to multi-armed bandits (MABs). We address this problem for MABs via a sharp analysis of KL-UCB using a novel peeling argument, which yields a $\tilde{O}(ηK\log^2T)$ upper bound: the first high-probability regret bound with linear dependence on $K$. Here, $T$ is the time horizon, $K$ is the number of arms, $η^{-1}$ is the regularization intensity, and $\tilde{O}$ hides all logarithmic factors except those involving $\log T$. The near-tightness of our analysis is certified by the first non-constant lower bound $Ω(ηK \log T)$, which follows from subtle hard-instance constructions and a tailored decomposition of the Bayes prior. Moreover, in the low-regularization regime (i.e., large $η$), we show that the KL-regularized regret for MABs is $η$-independent and scales as $\tildeΘ(\sqrt{KT})$. Overall, our results provide a thorough understanding of KL-regularized MABs across all regimes of $η$ and yield nearly optimal bounds in terms of $K$, $η$, and $T$.

Nima Shoghi, Yuxuan Liu, Yuning Shen et al.

Molecular dynamics (MD) simulations remain the gold standard for studying protein dynamics, but their computational cost limits access to biologically relevant timescales. Recent generative models have shown promise in accelerating simulations, yet they struggle with long-horizon generation due to architectural constraints, error accumulation, and inadequate modeling of spatio-temporal dynamics. We present STAR-MD (Spatio-Temporal Autoregressive Rollout for Molecular Dynamics), a scalable SE(3)-equivariant diffusion model that generates physically plausible protein trajectories over microsecond timescales. Our key innovation is a causal diffusion transformer with joint spatio-temporal attention that efficiently captures complex space-time dependencies while avoiding the memory bottlenecks of existing methods. On the standard ATLAS benchmark, STAR-MD achieves state-of-the-art performance across all metrics--substantially improving conformational coverage, structural validity, and dynamic fidelity compared to previous methods. STAR-MD successfully extrapolates to generate stable microsecond-scale trajectories where baseline methods fail catastrophically, maintaining high structural quality throughout the extended rollout. Our comprehensive evaluation reveals severe limitations in current models for long-horizon generation, while demonstrating that STAR-MD's joint spatio-temporal modeling enables robust dynamics simulation at biologically relevant timescales, paving the way for accelerated exploration of protein function.

Shiyuan Zhang, Qiwei Di, Xuheng Li et al.

Underdamped Langevin dynamics (ULD) is a widely-used sampler for Gibbs distributions $π\propto e^{-V}$, and is often empirically effective in high dimensions. However, existing non-asymptotic convergence guarantees for discretized ULD typically scale polynomially with the ambient dimension $d$, leading to vacuous bounds when $d$ is large. The main known dimension-free result concerns the randomized midpoint discretization in Wasserstein-2 distance (Liu et al.,2023), while dimension-independent guarantees for ULD discretizations in KL divergence have remained open. We close this gap by proving the first dimension-free KL divergence bounds for discretized ULD. Our analysis refines the KL local error framework (Altschuler et al., 2025) to a dimension-free setting and yields bounds that depend on $\mathrm{tr}(\mathbf{H})$, where $\mathbf{H}$ upper bounds the Hessian of $V$, rather than on $d$. As a consequence, we obtain improved iteration complexity for underdamped Langevin Monte Carlo relative to overdamped Langevin methods in regimes where $\mathrm{tr}(\mathbf{H})\ll d$.

Yifan Zhang, Yifeng Liu, Mengdi Wang et al.

The effectiveness of deep residual networks hinges on the identity shortcut connection. While this mechanism alleviates the vanishing-gradient problem, it also has a strictly additive inductive bias on feature transformations, limiting the network's ability to model complex hidden state transitions. In this paper, we introduce \textbf{Deep Delta Learning (DDL)}, which generalizes the shortcut from a fixed identity map to a learnable, state-dependent linear operator. The resulting Delta Operator is a rank-1 perturbation of the identity, $\mathbf{A}(\mathbf{X}) = \mathbf{I}- β(\mathbf{X})\mathbf{k} (\mathbf{X}) \mathbf{k} (\mathbf{X})^\top$, parameterized by a unit direction $\mathbf{k}(\mathbf{X})$ and a scalar gate $β(\mathbf{X})$. We provide a spectral analysis showing that $β(\mathbf{X})$ continuously interpolates the shortcut between identity ($β=0$), orthogonal projection ($β=1$), and Householder reflection ($β=2$). Furthermore, we rewrite the residual update as a synchronized rank-1 delta write: $β$ scales both the removal of the current $\mathbf{k}$-component and the injection of the new $\mathbf{k}$-component. This unification enables explicit control of the shortcut spectrum along a data-dependent direction while retaining stable training behavior. Empirically, replacing Transformer residual additions with DDL improves validation loss and perplexity, as well as downstream evaluation accuracy on language modeling tasks, with larger gains in the expanded-state setting.

Chenyang Zhang, Qingyue Zhao, Quanquan Gu et al.

Transformers have achieved great success across a wide range of applications, yet the theoretical foundations underlying their success remain largely unexplored. To demystify the strong capacities of transformers applied to versatile scenarios and tasks, we theoretically investigate utilizing transformers as students to learn from a class of teacher models. Specifically, the teacher models covered in our analysis include convolution layers with average pooling, graph convolution layers, and various classic statistical learning models, including a variant of sparse token selection models [Sanford et al., 2023, Wang et al., 2024] and group-sparse linear predictors [Zhang et al., 2025]. When learning from this class of teacher models, we prove that one-layer transformers with simplified "position-only'' attention can successfully recover all parameter blocks of the teacher models, thus achieving the optimal population loss. Building upon the efficient mimicry of trained transformers towards teacher models, we further demonstrate that they can generalize well to a broad class of out-of-distribution data under mild assumptions. The key in our analysis is to identify a fundamental bilinear structure shared by various learning tasks, which enables us to establish unified learning guarantees for these tasks when treating them as teachers for transformers.

Xiaohang Tang, Sangwoong Yoon, Seongho Son et al.

Self-play alignment has emerged as an effective approach for fine-tuning large language models (LLMs), formulating preference optimization as a two-player game. However, the regularization with respect to the reference policy, which is crucial for mitigating over-optimization, has been insufficiently investigated in self-play alignment. To study the impact of different regularization strategies, we propose \textbf{Regularized Self-Play Policy Optimization (RSPO)}, a general and modular framework that unifies prior methods and enables simple plug-and-play integration of various regularizers, meanwhile preserving convergence to Nash equilibrium of the corresponding regularized game.Our empirical study involving over $120$ fine-tuned Mistral-7B-Instruct models reveals that forward KL divergence regularization reduces response length, whereas reverse KL divergence markedly improves raw win rates. Crucially, RSPO regularized with a linear combination of forward and reverse KL divergence significantly boosts the length-controlled win rate on AlpacaEval-2 from $28.5\%$ (unregularized self-play, SPPO) to $35.4\%$, and consistently demonstrates superior performance on Arena-Hard, MT-Bench, ArmoRM scores, and response diversity. Combining simplicity, convergence guarantees, and significant empirical gains, RSPO offers a strong foundation for exploring regularized self-play in language model alignment.