Multiscale modeling of mechanisms for viral capsid assembly and polymorphism

描述(申请人提供)：在许多病毒的复制过程中，成百上千个蛋白质亚单位聚集在病毒核酸周围，形成一个称为衣壳的蛋白质外壳。在宿主体内，大多数病毒以惊人的保真度形成一个特定的结构；然而，最近的实验表明，衣壳可以以不同的大小和形态组装起来，以容纳不同大小的核酸、无机纳米粒子和聚阴离子。该项目将使用计算模型来确定病毒蛋白质及其货物的特征，使组装如此精确，同时又具有如此高的适应性。我们开发了病毒蛋白质和货物的简化表示法，范围从刚性球体到波动聚合物，再到模拟核酸。利用这些模型，我们将开发可实验测试的预测，以确定病毒蛋白动态包裹这些对象的机制，以及哪些因素将组装过程引导到特定的大小和形态。这些粗粒度的整体组装过程模型将通过原子分辨率模拟进行验证和指导，这些模拟检查病毒蛋白质的动态构象。

DESCRIPTION (provided by applicant): During the replication of many viruses, hundreds to thousands of protein subunits assemble around the viral nucleic acid to form a protein shell called a capsid. Within their host organism, most viruses form one particular structure with astonishing fidelity; yet, recent experiments demonstrate that capsids can assemble with different sizes and morphologies to accommodate nucleic acids, inorganic nanoparticles, and polyanions with different sizes. This project will use computational models to determine the features of viral proteins and their cargoes that enable assembly to be so precise and yet so adaptable. We develop simplified representations of viral proteins and cargoes that range from rigid spheres to fluctuating polymers to model nucleic acids. With these models we will develop experimentally testable predictions for the mechanisms by which viral proteins dynamically encapsidate these objects, and which factors direct the assembly process towards a particular size and morphology. These coarse-grained models of the overall assembly process will be validated and guided by atomic-resolution simulations that examine the dynamic conformations of viral proteins.