Generating diverse, all-atom conformational ensembles of dynamic proteins such as G-protein-coupled receptors (GPCRs) is critical for understanding their function, yet most generative models simplify atomic detail or ignore conformational diversity altogether.

As recommended by the NeurIPS dataset and benchmark track, we documented QM1B and intended uses through the Datasheets for Datasets framework [1]. The goal of dataset datasheets as outlined by [1] is to provide a standardized process for documentating datasets. The authors of [1] present a list of carefully selected questions which dataset authors should answer. We hope our answers to these questions will facilitate better communication between us (the dataset creators) and future users of QM1B. For what purpose was the dataset created? Prior gaussian-based Density Functional Theory (DFT) datasets contained fewer than 20 million training examples.

Sampling equilibrium molecular configurations from the Boltzmann distribution is a longstanding challenge. Boltzmann Generators (BGs) address this by combining exact-likelihood generative models with importance sampling, but their practical scalability is limited. Meanwhile, coarse-grained surrogates enable the modeling of larger systems by reducing effective dimensionality, yet often lack the reweighting process required to ensure asymptotically correct statistics. In this work, we propose Coarse-Grained Boltzmann Generators (CG-BGs), a principled framework that unifies scalable reduced-order modeling with the exactness of importance sampling. CG-BGs act in a coarse-grained coordinate space, using a learned potential of mean force (PMF) to reweight samples generated by a flow-based model. Crucially, we show that this PMF can be efficiently learned from rapidly converged data via force matching. Our results demonstrate that CG-BGs faithfully capture complex interactions mediated by explicit solvent within highly reduced representations, establishing a scalable pathway for the unbiased sampling of larger molecular systems.

Obtaining 3D conformations of realistic polyatomic molecules at the quantum chemistry level remains challenging, and although recent machine learning advances offer promise, predicting large-molecule structures still requires substantial computational effort. Here, we introduce StoL, a diffusion model-based framework that enables rapid and knowledge-free generation of large molecular structures from small-molecule data. Remarkably, StoL assembles molecules in a LEGO-style fashion from scratch, without seeing the target molecules or any structures of comparable size during training. Given a SMILES input, it decomposes the molecule into chemically valid fragments, generates their 3D structures with a diffusion model trained on small molecules, and assembles them into diverse conformations. This fragment-based strategy eliminates the need for large-molecule training data while maintaining high scalability and transferability. By embedding chemical principles into key steps, StoL ensures faster convergence, chemically rational structures, and broad configurational coverage, as confirmed against DFT calculations.

Neural transport augmented samplers have been subsequently extended by Hoffman et al. (2019) While, Duncan et al. (2019) have studied the Another contribution of this paper is learning equivariant Energy-Based Models using equivariant Stein variational gradient descent. Energy Based Models have witnessed a revival recently. As far as the authors are aware. Figure 8: Recommended to view in color . Translucent yellow dots represent the distribution.

As recommended by the NeurIPS dataset and benchmark track, we documented QM1B and intended uses through the Datasheets for Datasets framework [1]. The goal of dataset datasheets as outlined by [1] is to provide a standardized process for documentating datasets. The authors of [1] present a list of carefully selected questions which dataset authors should answer. We hope our answers to these questions will facilitate better communication between us (the dataset creators) and future users of QM1B. For what purpose was the dataset created? Prior gaussian-based Density Functional Theory (DFT) datasets contained fewer than 20 million training examples.

We thank the reviewers for the thoughtful feedback in these difficult times caused by the global COVID-19 pandemic. QM9 is used for training, the model must be based on LCAO, and QDF achieved high extrapolation performance. We emphasize that even this LDA-like HK map achieved high extrapolation performance. We will address this in future work. Of course, QDF can be proposed without a comparison to GCN.

Generating diverse, all-atom conformational ensembles of dynamic proteins such as G-protein-coupled receptors (GPCRs) is critical for understanding their function, yet most generative models simplify atomic detail or ignore conformational diversity altogether. We present latent diffusion for full protein generation (LD-FPG), a framework that constructs complete all-atom protein structures, including every side-chain heavy atom, directly from molecular dynamics (MD) trajectories. LD-FPG employs a Chebyshev graph neural network (ChebNet) to obtain low-dimensional latent embeddings of protein conformations, which are processed using three pooling strategies: blind, sequential and residue-based. A diffusion model trained on these latent representations generates new samples that a decoder, optionally regularized by dihedral-angle losses, maps back to Cartesian coordinates. Using D2R-MD, a 2-microsecond MD trajectory (12 000 frames) of the human dopamine D2 receptor in a membrane environment, the sequential and residue-based pooling strategy reproduces the reference ensemble with high structural fidelity (all-atom lDDT of approximately 0.7; C-alpha-lDDT of approximately 0.8) and recovers backbone and side-chain dihedral-angle distributions with a Jensen-Shannon divergence of less than 0.03 compared to the MD data. LD-FPG thereby offers a practical route to system-specific, all-atom ensemble generation for large proteins, providing a promising tool for structure-based therapeutic design on complex, dynamic targets. The D2R-MD dataset and our implementation are freely available to facilitate further research.