Daily Papers

Developing controllers capable of completing a wide range of tasks in a natural and life-like manner is a key challenge in enabling practical applications of physics-based character animation. In this work, we introduce Generative Pretrained Controllers (GPC), which leverage tokenization and next-token modeling to create general-purpose, reusable generative controllers from large-scale motion datasets. Our framework utilizes end-to-end reinforcement learning to jointly optimize a "motion vocabulary", modeled via Finite Scalar Quantization (FSQ), along with a corresponding control policy that can map the discrete codes to physics-based controls. After the "codebook" has been learned, the underlying structure of this large vocabulary is modeled by training a GPT-style autoregressive transformer, leading to a powerful generative controller that generates controls for a physically simulated character by performing next-token prediction. Once the generative controller has been trained, we propose a suite of adaptation techniques for finetuning the controller for new downstream tasks. Our proposed framework greatly simplifies the training process compared to previous tokenized methods, and achieves a 99.98% success rate in reproducing a vast corpus of motion clips. The generative controller exhibits a variety of natural emergent behaviors, such as responsive behaviors to perturbations and recovery behaviors after falling. This results in highly robust general purpose controllers for a variety of downstream applications.

G protein-coupled receptors (GPCRs) govern diverse physiological processes and are central to modern pharmacology. Yet discovering GPCR modulators remains challenging because receptor activation often arises from complex allosteric effects rather than direct binding affinity, and conventional assays are slow, costly, and not optimized for capturing these dynamics. Here we present GPCR-Filter, a deep learning framework specifically developed for GPCR modulator discovery. We assembled a high-quality dataset of over 90,000 experimentally validated GPCR-ligand pairs, providing a robust foundation for training and evaluation. GPCR-Filter integrates the ESM-3 protein language model for high-fidelity GPCR sequence representations with graph neural networks that encode ligand structures, coupled through an attention-based fusion mechanism that learns receptor-ligand functional relationships. Across multiple evaluation settings, GPCR-Filter consistently outperforms state-of-the-art compound-protein interaction models and exhibits strong generalization to unseen receptors and ligands. Notably, the model successfully identified micromolar-level agonists of the 5-HT1A receptor with distinct chemical frameworks. These results establish GPCR-Filter as a scalable and effective computational approach for GPCR modulator discovery, advancing AI-assisted drug development for complex signaling systems.