隐式生物膜模型及E蛋白折叠模拟

Computer simulation of SARS coronavirus-associated E protein's folding in biological membrane

受计算速度所限,现有生物膜模拟多集中于膜内多肽链片断,对膜两侧的多肽链片断关注较少.通过构建隐式生物膜模型,在格子空间中针对传染性非典型肺炎冠状病毒E蛋白的全序列进行模拟研究.结果表明,E蛋白在折叠过程中存在两个明显的热力学转变:从无规线团开始,生物膜内较强的氢键相互作用促使螺旋形成,导致coil-helix转变;在疏水相互作用下,膜两侧水溶液中的多肽链片断发生坍塌,导致coil-globule转变;最后形成稳定的跨膜构象,且跨膜序列与已有的预测结果基本符合.相关模拟手段体现了很高的计算效率,为后续的膜蛋白聚集体模拟研究提供了可行方法.

With the limitation of computing speed, most of simulation researches focus on the polypeptide segment inside membrane, losing sight of the parts outside membrane. Via the construction of implicit biological membrane, a computer simulation of severe acute respiratory syndromes coronavirus associated E protein in its complete length was performed in lattice space. The research results revealed two distinct thermodynamic transitions in the E protein＇s folding process. During the first transition, the initial random coil became a-helix and the coil-helix transition occurred due to the strong hydrogen bonding interaction in biological membrane. In the second transition, the polypeptide segment outside of the membrane collapsed, and the coil-globule transition took place because of the residue＇s hydrophobic interaction in solution. Finally, a stable transmembrane conformation was shaped and the sequence partition was in accordance with other prediction for E protein. In addition, our simulation method exhibited high computational efficiency, thus providing feasibility for the simulation of homo-oligomeric bundles of transmembrane protein.