Title: Hierarchical Multi-Scale Molecular Conformer Generation with Structural Awareness
Primary area: generative models
Keywords: Molecular conformer generation, Generative models

Abstract: Molecular conformer generation is a fundamental task for drug discovery and material design. Although deep generative models have progressed in this area, existing methods often overlook the hierarchical structural organization inherent to molecules, leading to poor-quality generated conformers. To address this challenge, we demonstrate that capturing the spatial arrangement of key substructures, such as scaffolds, is essential, as they serve as anchors that define the overall molecular distribution. In this paper, we propose a hierarchical multi-scale molecular conformer generation framework (MSGEN), designed to enhance key substructure awareness by leveraging spatially informed guidance. Our framework initiates the generation process from coarse-grained key substructures, progressively refining the conformer by utilizing these coarser-scale structures as conditional guidance for subsequent finer-scale stages. To bridge scale discrepancies between stages, we introduce a molecular upsampling technique that aligns the structural scales, ensuring smooth propagation of geometric guidance. Extensive experiments on standard benchmarks demonstrate that our framework integrates seamlessly with a wide range of existing molecular generative models and consistently generates more stable and chemically plausible molecular conformers.