RL for Generative Models

Protein generative models have shown remarkable promise in protein design, yet their success rates remain constrained by reliance on curated sequence-structure datasets and by misalignment between supervised objectives and real design goals. We present ProteinZero, an online reinforcement learning framework for inverse folding models that enables scalable, automated, and continuous self-improvement with computationally efficient feedback. ProteinZero employs a reward pipeline that combines structural guidance from ESMFold with a novel self-derived ddG predictor, providing stable multi-objective signals while avoiding the prohibitive cost of physics-based methods. To ensure robustness in online RL, we further introduce a novel embedding-level diversity regularizer that mitigates mode collapse and promotes sequence-level diversity among generated designs. Within a general RL formulation balancing multi-reward optimization, KL-divergence from a reference model, and diversity regularization, ProteinZero achieves robust improvements across designability, predicted stability, recovery, and diversity. On the CATH-4.3 benchmark, it consistently outperforms state-of-the-art baselines including ProteinMPNN, ESM-IF, and InstructPLM, reducing design failure rates by 36-48% and achieving success rates above 90% across diverse folds. Importantly, a complete RL run can be executed on a single 8xGPU node within three days, including reward computation and data generation. These results indicate that efficient online RL fine-tuning can complement supervised pretraining by allowing protein generative models to evolve continuously from their own outputs and optimize multiple design objectives without labeled data, opening new possibilities for exploring the vast protein design space. Code and model checkpoints are available at https://github.com/ziwenwang28/ProteinZero.

This paper builds bridges between two families of probabilistic algorithms: (hierarchical) variational inference (VI), which is typically used to model distributions over continuous spaces, and generative flow networks (GFlowNets), which have been used for distributions over discrete structures such as graphs. We demonstrate that, in certain cases, VI algorithms are equivalent to special cases of GFlowNets in the sense of equality of expected gradients of their learning objectives. We then point out the differences between the two families and show how these differences emerge experimentally. Notably, GFlowNets, which borrow ideas from reinforcement learning, are more amenable than VI to off-policy training without the cost of high gradient variance induced by importance sampling. We argue that this property of GFlowNets can provide advantages for capturing diversity in multimodal target distributions.

Generative Flow Networks (GFlowNets) have shown promising potential to generate high-scoring candidates with probability proportional to their rewards. As existing GFlowNets freely explore in state space, they encounter significant convergence challenges when scaling to large state spaces. Addressing this issue, this paper proposes to restrict the exploration of actor. A planner is introduced to partition the entire state space into overlapping partial state spaces. Given their limited size, these partial state spaces allow the actor to efficiently identify subregions with higher rewards. A heuristic strategy is introduced to switch partial regions thus preventing the actor from wasting time exploring fully explored or low-reward partial regions. By iteratively exploring these partial state spaces, the actor learns to converge towards the high-reward subregions within the entire state space. Experiments on several widely used datasets demonstrate that \modelname converges faster than existing works on large state spaces. Furthermore, \modelname not only generates candidates with higher rewards but also significantly improves their diversity.

Native visual reasoning treats visual generation as the medium of reasoning itself: visual states (i.e. images and videos) are not merely inputs to be understood or outputs to be rendered, but first-class substrates for problem solving beyond language. Yet progress remains bottlenecked by the lack of scalable training tasks, reliable feedback, and controlled comparisons across generative substrates. In this work, we introduce VBVR-Pro, a closed-loop testbed that makes native visual reasoning through generation trainable, verifiable, optimizable, and experimentally controllable. 1) Task scaling. VBVR-Pro turns visual reasoning into a controlled task space of 300 procedurally generated tasks. Models trained on VBVR-Pro show strong transfer beyond the proposed suite across seven external visual reasoning benchmarks such as RISE-Video, MME-CoF-Pro, and BabyVision. 2) Verifiable rewards. VBVR-Pro provides verifiable reward scorers for task-grounded evaluation. Through a systematic study of leading MLLMs as judges, we identify recurring failure modes of the prevalent VLM-as-a-judge paradigm. In contrast, the proposed scorers are grounded in deterministic, task-specific rules, achieve fine-grained alignment with human judgments. Importantly, they serve as reliable reward signals for large-scale multi-task reinforcement learning and demonstrate stronger post-RL performance across visual reasoning tasks. 3) Mechanism study. VBVR-Pro enables controlled modality studies across more than 30 image, video, and interleaved generators. Our analysis shows that video generation remains strongest for tasks requiring persistent spatiotemporal state tracking, while interleaved generation provides a compute-efficient alternative. Critically, ablations and probing suggest the presence of vision-native trajectories that are crucial to visual reasoning. We release all data, models, scorers, and code.