Protocols for Requirement-Driven Protein Design in the Rosetta Modeling Program,Journal of Chemical Information and Modeling

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Protocols for Requirement-Driven Protein Design in the Rosetta Modeling Program
Journal of Chemical Information and Modeling ( IF 5.6 ) Pub Date : 2018-04-16 00:00:00 , DOI: 10.1021/acs.jcim.8b00060
Sharon L. Guffy ₁ , Frank D. Teets ₁ , Minnie I. Langlois ₁ , Brian Kuhlman _{1,

2}

Affiliation

We have developed a set of protocols in the molecular modeling program Rosetta for performing requirement-driven protein design. First, the user specifies a set of structural features that need to be present in the designed protein. These requirements can be general (e.g., “create a protein with five helices”), or they can be very specific and require the correct placement of a set of amino acids to bind a ligand. Next, a large set of protein models are generated that satisfy the design requirements. The models are built using a method that we recently introduced into Rosetta, called SEWING, that rapidly assembles novel protein backbones by combining pieces of naturally occurring proteins. In the last step of the process, rotamer-based sequence optimization and backbone refinement are performed with Rosetta, and a variety of quality metrics are used to pick sequences for experimental characterization. Here we describe the input files and user options needed to run SEWING and perform requirement-driven design and provide detailed instructions for two specific applications of the process: the design of new structural elements at a protein–protein interface and the design of ligand binding sites.

中文翻译：

Rosetta建模程序中需求驱动蛋白设计的协议

我们已经在分子建模程序Rosetta中开发了一组协议，用于执行需求驱动的蛋白质设计。首先，用户指定了一组在设计的蛋白质中必须存在的结构特征。这些要求可能很笼统（例如，“用五个螺旋生成蛋白质”），或者可能非常特殊，并且需要正确放置一组氨基酸以结合配体。接下来，将生成满足设计要求的大量蛋白质模型。这些模型是使用我们最近引入Rosetta的一种称为SEWING的方法构建的，该方法通过结合自然存在的蛋白质片段来快速组装新的蛋白质骨架。在该过程的最后一步，使用Rosetta执行基于旋转异构体的序列优化和主链优化，并且使用各种质量指标来挑选序列进行实验表征。在这里，我们描述了运行SEWING和执行需求驱动的设计所需的输入文件和用户选项，并为该过程的两个特定应用提供了详细说明：蛋白质-蛋白质界面的新结构元件的设计以及配体结合位点的设计。

更新日期：2018-04-16

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