T.C. Jenkins Department of Biophysics and Program in Molecular Biophysics, Johns Hopkins University, Baltimore, Maryland, USA.
US District Court for the District of Delaware, 844 N. King Street, Wilmington, Delaware, USA.
Protein Sci. 2021 Jan;30(1):168-186. doi: 10.1002/pro.3977. Epub 2020 Nov 2.
A collection of programs is presented to analyze the thermodynamics of folding of linear repeat proteins using a 1D Ising model to determine intrinsic folding and interfacial coupling free energies. Expressions for folding transitions are generated for a series of constructs with different repeat numbers and are globally fitted to transitions for these constructs. These programs are designed to analyze Ising parameters for capped homopolymeric consensus repeat constructs as well as heteropolymeric constructs that contain point substitutions, providing a rigorous framework for analysis of the effects of mutation on intrinsic and directional (i.e., N- vs. C-terminal) interfacial coupling free-energies. A bootstrap analysis is provided to estimate parameter uncertainty as well as correlations among fitted parameters. Rigorous statistical analysis is essential for interpreting fits using the complex models required for Ising analysis of repeat proteins, especially heteropolymeric repeat proteins. Programs described here are available at https://github.com/barricklab-at-jhu/Ising_programs.
本文提出了一系列程序，使用一维伊辛模型来分析线性重复蛋白的折叠热力学，以确定固有折叠和界面耦合自由能。为一系列具有不同重复数目的构建体生成折叠跃迁表达式，并将其全局拟合到这些构建体的跃迁。这些程序旨在分析带有帽状同聚共识重复构建体的伊辛参数，以及含有点取代的杂聚构建体，为分析突变对固有和定向（即 N- 端与 C- 端）界面耦合自由能的影响提供了严格的框架。提供了自举分析来估计参数不确定性以及拟合参数之间的相关性。对于使用伊辛分析重复蛋白（尤其是杂聚重复蛋白）所需的复杂模型进行拟合，严格的统计分析是必不可少的。此处描述的程序可在 https://github.com/barricklab-at-jhu/Ising_programs 上获得。
