Atomistic modelling of scattering data in the Collaborative Computational Project for Small Angle Scattering (CCP-SAS).
Atomistic modelling of scattering data in the Collaborative Computational Project for Small Angle Scattering (CCP-SAS).
复制标题
DOI：
10.1107/s160057671601517x
复制
发表时间：
2016-12-01
影响因子：
6.1
通讯作者：
Curtis JE
中科院分区：
文献类型：
--
作者：
Perkins SJ;Wright DW;Zhang H;Brookes EH;Chen J;Irving TC;Krueger S;Barlow DJ;Edler KJ;Scott DJ;Terrill NJ;King SM;Butler PD;Curtis JE
CCP-SAS项目目前正在为X射线和中子小角散射数据的原子和粗粒分子建模开发软件。它的计算框架进行了描述，以及在生物学和软物质中的应用。目前的计算机模拟的能力提供了一个独特的机会，模型小角散射（SAS）的数据在原子水平上，并包括其他结构的限制，从分子和原子能晶体学，电子显微镜和NMR。这扩展了溶液散射的能力，并为所研究系统的物理和化学提供了更深入的见解。然而，实现这一潜力需要将实验数据与新一代建模软件相结合。为实现这一目标，CCP-SAS协作（http：//www.ccpsas.org/）正在开发开放源码、高通量和用户友好型软件，用于对散射数据进行原子和粗粒度分子建模。强大的最先进的分子模拟引擎和分子动力学和蒙特卡罗力场提供了从小角度散射数据推断的解决方案结构的约束，其中包含了系统的已知物理化学。该软件套件的实施涉及一种分层方法，其中GenApp提供了在标准和高性能计算硬件上运行应用程序的部署基础设施，SASSIE提供了一个工作流程框架，可以将模块插入其中以准备结构，进行模拟，计算理论散射数据并将结果与实验数据进行比较。GenApp制作了可访问的基于网络的前端，称为SASSIE-web，GenApp和SASSIE还提供社区SAS代码。通过案例研究说明了应用：（i）以HIV-1 Gag、MASP和泛素为例的2 - 6结构域蛋白质中的结构域间柔性;（ii）人IgG 2和IgA 1抗体中的铰链构象;（iii）六聚体蛋白Hfq和mRNA之间形成的复合物;以及（iv）合成的“瓶刷”聚合物。
The CCP-SAS project is currently developing software for the atomistic and coarse-grained molecular modelling of X-ray and neutron small-angle scattering data. Its computational framework is described, alongside applications in biology and soft matter. The capabilities of current computer simulations provide a unique opportunity to model small-angle scattering (SAS) data at the atomistic level, and to include other structural constraints ranging from molecular and atomistic energetics to crystallography, electron microscopy and NMR. This extends the capabilities of solution scattering and provides deeper insights into the physics and chemistry of the systems studied. Realizing this potential, however, requires integrating the experimental data with a new generation of modelling software. To achieve this, the CCP-SAS collaboration (http://www.ccpsas.org/) is developing open-source, high-throughput and user-friendly software for the atomistic and coarse-grained molecular modelling of scattering data. Robust state-of-the-art molecular simulation engines and molecular dynamics and Monte Carlo force fields provide constraints to the solution structure inferred from the small-angle scattering data, which incorporates the known physical chemistry of the system. The implementation of this software suite involves a tiered approach in which GenApp provides the deployment infrastructure for running applications on both standard and high-performance computing hardware, and SASSIE provides a workflow framework into which modules can be plugged to prepare structures, carry out simulations, calculate theoretical scattering data and compare results with experimental data. GenApp produces the accessible web-based front end termed SASSIE-web, and GenApp and SASSIE also make community SAS codes available. Applications are illustrated by case studies: (i) inter-domain flexibility in two- to six-domain proteins as exemplified by HIV-1 Gag, MASP and ubiquitin; (ii) the hinge conformation in human IgG2 and IgA1 antibodies; (iii) the complex formed between a hexameric protein Hfq and mRNA; and (iv) synthetic ‘bottlebrush’ polymers.