Journal Article

A variational expectation-maximization framework for balanced multi-scale learning of protein and drug interactions

Zheng, Shuangjia, Yuan, Qianmu, Wang, Zhen, Lu, Yutong, Liu, Deqin, Rao, Jiahua, Xie, Jiancong, Yang, Yuedong

2024

Overview

Protein functions are characterized by interactions with proteins, drugs, and other biomolecules. Understanding these interactions is essential for deciphering the molecular mechanisms underlying biological processes and developing new therapeutic strategies. Current computational methods mostly predict interactions based on either molecular network or structural information, without integrating them within a unified multi-scale framework. While a few multi-view learning methods are devoted to fusing the multi-scale information, these methods tend to rely intensively on a single scale and under-fitting the others, likely attributed to the imbalanced nature and inherent greediness of multi-scale learning. To alleviate the optimization imbalance, we present MUSE, a multi-scale representation learning framework based on a variant expectation maximization to optimize different scales in an alternating procedure over multiple iterations. This strategy efficiently fuses multi-scale information between atomic structure and molecular network scale through mutual supervision and iterative optimization. MUSE outperforms the current state-of-the-art models not only in molecular interaction (protein-protein, drug-protein, and drug-drug) tasks but also in protein interface prediction at the atomic structure scale. More importantly, the multi-scale learning framework shows potential for extension to other scales of computational drug discovery. Multi-scale learning still struggles with imbalanced information and greedy characteristics. Here the authors present MUSE, an Expectation-Maximization-based multi-scale framework, improving predictions across molecular interactions and atomic interfaces.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/114/2401 / 631/114/2784 / 631/1647/338/2248 / Algorithms / Atomic structure / Biological activity / Biomolecules / Computational Biology - methods / Computer applications / Drug interaction / Drug Interactions / Humanities and Social Sciences / Humans / Learning / Machine Learning / Maximization / Molecular interactions / Molecular modelling / Molecular structure / multidisciplinary / Optimization / Pharmaceutical Preparations - chemistry / Pharmaceutical Preparations - metabolism / Protein Binding / Proteins / Proteins - chemistry / Proteins - metabolism / Representation learning / Science / Science (multidisciplinary)