MOES-Pred: Molecular Structural Representation Learning by Adaptive Energy-Sentinel Vibration for Generalized Property Prediction

摘要

Molecular property prediction from 3D structures is fundamentally constrained by the scarcity of labeled data. To address this challenge, researchers have adapted various self-supervised pre-training methods from computer vision and natural language processing; however, these approaches often neglect the fundamental physical principles unique to molecular systems. When grounded in physical principles, denoising pre-training can be formally shown to be equivalent to learning molecular force fields.However, existing methods uniformly apply a uniform noise scheme across all molecules, which introduces systematic bias in molecular distribution modeling. To overcome this limitation, we propose MOES-Pred, a novel denoising pre-training framework that employs an energy sentinel mechanism to dynamically adjust molecule-specific noise perturbations. By incorporating chemical prior knowledge, we design molecule-specific noising strategies that expand conformational sampling coverage and improve the fidelity of molecular distribution modeling. Extensive experiments demonstrate that MOES-Pred consistently surpasses existing methods, achieving state-of-the-art performance on both force prediction tasks and downstream quantum chemical property predictions.