CAS-MPG Partner Institute and Key Laboratory for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
BMC Bioinformatics. 2011 Apr 18;12:101. doi: 10.1186/1471-2105-12-101.
The way mechanical stress is distributed inside and propagated by proteins and other biopolymers largely defines their function. Yet, determining the network of interactions propagating internal strain remains a challenge for both, experiment and theory. Based on molecular dynamics simulations, we developed force distribution analysis (FDA), a method that allows visualizing strain propagation in macromolecules.
To be immediately applicable to a wide range of systems, FDA was implemented as an extension to Gromacs, a commonly used package for molecular simulations. The FDA code comes with an easy-to-use command line interface and can directly be applied to every system built using Gromacs. We provide an additional R-package providing functions for advanced statistical analysis and presentation of the FDA data.
Using FDA, we were able to explain the origin of mechanical robustness in immunoglobulin domains and silk fibers. By elucidating propagation of internal strain upon ligand binding, we previously also successfully revealed the functionality of a stiff allosteric protein. FDA thus has the potential to be a valuable tool in the investigation and rational design of mechanical properties in proteins and nano-materials.
机械应力在蛋白质和其他生物聚合物中的分布方式和传播方式在很大程度上决定了它们的功能。然而，确定内部应变的相互作用网络对于实验和理论来说仍然是一个挑战。基于分子动力学模拟，我们开发了力分布分析（FDA）方法，该方法可以可视化大分子中的应变传播。
为了立即适用于广泛的系统，FDA 被实现为 Gromacs 的扩展，Gromacs 是用于分子模拟的常用软件包。FDA 代码带有一个易于使用的命令行界面，可以直接应用于使用 Gromacs 构建的每个系统。我们还提供了一个额外的 R 包，提供用于高级统计分析和 FDA 数据表示的功能。
使用 FDA，我们能够解释免疫球蛋白结构域和丝纤维的机械鲁棒性的起源。通过阐明配体结合时内部应变的传播，我们之前还成功揭示了一种刚性别构蛋白的功能。因此，FDA 有可能成为研究和合理设计蛋白质和纳米材料机械性能的有用工具。
