Generative models for structure-based drug design (SBDD) have shown promising results in recent years. Existing works mainly focus on how to generate molecules with higher binding affinity, ignoring the feasibility prerequisites for generated 3D poses and resulting in false positives. We conduct thorough studies on key factors of ill-conformational problems when applying autoregressive methods and diffusion to SBDD, including mode collapse and hybrid continuous-discrete space. In this paper, we introduce MolCRAFT, the first SBDD model that operates in the continuous parameter space, together with a novel noise reduced sampling strategy. Empirical results show that our model consistently achieves superior performance in binding affinity with more stable 3D structure, demonstrating our ability to accurately model interatomic interactions. To our best knowledge, MolCRAFT is the first to achieve reference-level Vina Scores (-6.59 kcal/mol) with comparable molecular size, outperforming other strong baselines by a wide margin (-0.84 kcal/mol). Code is available at https://github.com/AlgoMole/MolCRAFT.
Advanced generative model (e.g., diffusion model) derived from simplified continuity assumptions of data distribution, though showing promising progress, has been difficult to apply directly to geometry generation applications due to the multi-modality and noise-sensitive nature of molecule geometry. This work introduces Geometric Bayesian Flow Networks (GeoBFN), which naturally fits molecule geometry by modeling diverse modalities in the differentiable parameter space of distributions. GeoBFN maintains the SE-(3) invariant density modeling property by incorporating equivariant inter-dependency modeling on parameters of distributions and unifying the probabilistic modeling of different modalities. Through optimized training and sampling techniques, we demonstrate that GeoBFN achieves state-of-the-art performance on multiple 3D molecule generation benchmarks in terms of generation quality (90.87% molecule stability in QM9 and 85.6% atom stability in GEOM-DRUG. GeoBFN can also conduct sampling with any number of steps to reach an optimal trade-off between efficiency and quality (e.g., 20-times speedup without sacrificing performance).
Large Language Models (LLMs) have demonstrated remarkable capabilities across various tasks, yet they face significant challenges in embodied task planning scenarios that require continuous environmental understanding and action generation. Existing approaches generate open-loop action scripts based on static knowledge, making it difficult to learn causal relationships between actions and environmental feedback, particularly in partially observable environments. We introduce Embodied Planner-R1, a novel outcome-driven reinforcement learning framework that enables LLMs to develop interactive capabilities through autonomous exploration with minimal supervision. Our framework incorporates three key innovations: (1) Without human annotations, we employ pure reinforcement learning with group rollout, incorporating in-environment interaction through parallel exploration; (2) completion-driven sparse reward; and (3) Interactive Policy Optimization (IPO) for efficient learning from grouped trajectories. Across two challenging text-based Embodied planning benchmarks, Embodied Planner-R1 achieves impressive completion rates of 97.78% on ALFWorld and 79.92% on ScienceWorld, surpassing prior methods by a large margin, and suffers only a -3.66% drop in previously unseen environments, evidencing strong generalization.