鱼鹰：具有集成、灵活性和可验证算法的蛋白质设计
OSPREY: protein design with ensembles, flexibility, and provable algorithms.
作者信息
Gainza Pablo, Roberts Kyle E, Georgiev Ivelin, Lilien Ryan H, Keedy Daniel A, Chen Cheng-Yu, Reza Faisal, Anderson Amy C, Richardson David C, Richardson Jane S, Donald Bruce R
机构信息
Department of Computer Science, Duke University, Durham, North Carolina, USA.
出版信息
Methods Enzymol. 2013;523:87-107. doi: 10.1016/B978-0-12-394292-0.00005-9.
UNLABELLED
We have developed a suite of protein redesign algorithms that improves realistic in silico modeling of proteins. These algorithms are based on three characteristics that make them unique: (1) improved flexibility of the protein backbone, protein side-chains, and ligand to accurately capture the conformational changes that are induced by mutations to the protein sequence; (2) modeling of proteins and ligands as ensembles of low-energy structures to better approximate binding affinity; and (3) a globally optimal protein design search, guaranteeing that the computational predictions are optimal with respect to the input model. Here, we illustrate the importance of these three characteristics. We then describe OSPREY, a protein redesign suite that implements our protein design algorithms. OSPREY has been used prospectively, with experimental validation, in several biomedically relevant settings. We show in detail how OSPREY has been used to predict resistance mutations and explain why improved flexibility, ensembles, and provability are essential for this application.
AVAILABILITY
OSPREY is free and open source under a Lesser GPL license. The latest version is OSPREY 2.0. The program, user manual, and source code are available at www.cs.duke.edu/donaldlab/software.php.
CONTACT
未标注
我们开发了一套蛋白质重新设计算法，可改进蛋白质的真实计算机模拟。这些算法基于三个使其独特的特性：（1）提高蛋白质主链、蛋白质侧链和配体的灵活性，以准确捕捉由蛋白质序列突变引起的构象变化；（2）将蛋白质和配体建模为低能量结构的集合，以更好地近似结合亲和力；（3）进行全局最优蛋白质设计搜索，确保计算预测相对于输入模型是最优的。在此，我们阐述这三个特性的重要性。然后我们描述了OSPREY，一个实现我们蛋白质设计算法的蛋白质重新设计套件。OSPREY已在多个与生物医学相关的场景中进行了前瞻性使用，并经过实验验证。我们详细展示了OSPREY如何用于预测抗性突变，并解释了为何改进的灵活性、集合和可证性对于此应用至关重要。
可用性
OSPREY根据较小通用公共许可证（Lesser GPL license）免费开源。最新版本是OSPREY 2.0。该程序、用户手册和源代码可在www.cs.duke.edu/donaldlab/software.php获取。
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