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

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.