Despite tremendous efforts, the exact structure of SARS-CoV-2 and related betacoronaviruses remains elusive. SARS-CoV-2 envelope is a key structural component of the virion that encapsulates viral RNA. It is composed of three structural proteins, spike, membrane (M), and envelope, which interact with each other and with the lipids acquired from the host membranes. Here, we developed and applied an integrative multi-scale computational approach to model the envelope structure of SARS-CoV-2 with near atomistic detail, focusing on studying the dynamic nature and molecular interactions of its most abundant, but largely understudied, M protein. The molecular dynamics simulations allowed us to test the envelope stability under different configurations and revealed that the M dimers agglomerated into large, filament-like, macromolecular assemblies with distinct molecular patterns. These results are in good agreement with current experimental data, demonstrating a generic and versatile approach to model the structure of a virus de novo.

尽管付出了巨大努力，但 SARS-CoV-2 和相关 β 冠状病毒的确切结构仍然难以捉摸。SARS-CoV-2 包膜是封装病毒 RNA 的病毒体的关键结构成分。它由三种结构蛋白组成，刺突蛋白、膜 (M) 和包膜，它们相互作用并与从宿主膜获得的脂质相互作用。在这里，我们开发并应用了一种综合的多尺度计算方法来模拟具有近原子细节的 SARS-CoV-2 的包膜结构，重点研究其最丰富但未被充分研究的 M 蛋白的动态性质和分子相互作用。分子动力学模拟使我们能够测试不同配置下的包络稳定性，并揭示 M 二聚体聚集成大的、丝状的，具有不同分子模式的大分子组装体。这些结果与当前的实验数据非常吻合，展示了一种通用且通用的病毒结构建模方法从头开始