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Protein Design: Toward Functional Metalloenzymes

机译:蛋白质设计:走向功能性金属酶

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Protein design is a valuable tool for understanding the fundamental factors that dictate protein structure and function. The field of protein design has seen significant progress over the past 30 years, with a growing range of applications in areas of research from fundamental biochemistry to biotechnology and medicine. Protein design is no trivial task. It is an ultimate test of our understanding of structure-function relationships and requires a combined knowledge of physics, chemistry, and biology. Evolution is nature's method of designing proteins, which has been very effective in producing scaffolds with exquisite structural details, breath-taking efficiency, and high selectivity. Rapid advancement of computer applications in biotechnology now enables one to model the evolution of a particular protein on a human time scale, instead of an evolutionary time scale; however, it is still quite a challenge to select an optimal solution from the enormous amount of mutations and to understand how these selective factors relate to the function of the protein. From the early examples of designing polypeptides or proteins that are stable in aqueous environments to today's novel functional metalloproteins, protein design has advanced to a stage where it is possible to create structures never before seen in nature, with functions not found in nature and novel sequences not derived from nature while exhibiting desired properties.
机译:蛋白质设计是了解理解决定蛋白质结构和功能的基本因素的宝贵工具。在过去的30年中,蛋白质设计领域取得了重大进展,在从基础生物化学到生物技术和医学的研究领域中,其应用范围不断扩大。蛋白质设计不是一件容易的事。这是对我们对结构-功能关系的理解的最终检验,并且需要结合物理学,化学和生物学知识。进化是大自然设计蛋白质的方法,在生产具有精美结构细节,呼吸效率和高选择性的支架方面非常有效。现在,生物技术中计算机应用的飞速发展使人们可以在人类时间尺度上而不是在进化时间尺度上模拟特定蛋白质的进化。然而,从大量的突变中选择最佳的解决方案并了解这些选择因子与蛋白质功能之间的关系仍然是一个挑战。从设计在水性环境中稳定的多肽或蛋白质的早期实例到今天的新型功能性金属蛋白,蛋白质设计已发展到可以创建自然界中从未见过的结构,具有自然界中未发现的功能和新颖序列的阶段在表现出所需特性的同时不衍生自自然。

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