人工智能为膜蛋白造“装甲” 浙大跨学科团队突破膜蛋白设计全球瓶颈

Core Insights - Zhejiang University has published its first article in "Nature," introducing a novel technology called GPCR Exoframe Modulator (GEM) on February 17, coinciding with the Lunar New Year [1] Group 1: Importance of GPCR - G protein-coupled receptors (GPCRs) are the largest signal receptors on human cell membranes, regulating critical life processes such as sensation, emotion, cardiovascular function, and metabolism [2] - Genetic mutations can cause structural disruptions in GPCRs, leading to signal transmission failures and various diseases, including diabetes insipidus, Parkinson's-like diseases, and Alzheimer's [2] - Traditional drugs targeting GPCRs are limited to the "orthosteric pocket," which only allows for basic activation or inhibition, resulting in limited therapeutic efficacy [2] Group 2: Research and Development of GEM - The research team, led by Professor Zhang Yan, aims to design "exoframe proteins" for GPCRs, leveraging over 20 years of research and collaboration with AI experts [3] - GEM employs an "exoskeletal" modulation approach, directly affecting the transmembrane domain of GPCRs to finely tune signal output, expanding the classic seven transmembrane helices to nine, eleven, or even thirteen [4] - The breakthrough involves an AI-driven membrane protein design system that scans GPCR surfaces and generates protein structures with atomic-level precision [4] Group 3: Advantages and Future Applications of GEM - Compared to traditional drugs, GEM offers programmable and precise modulation capabilities, allowing for multidimensional signal regulation and the potential to create biological "logic gates" for signal reprogramming [5] - The team has established an AI-driven platform for membrane protein functional design, aiming to optimize AI models and expand GEM's applications across various diseases, facilitating clinical translation [5]