Strategies for Increasing Protein Stability
Strategies for Increasing Protein Stability
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DOI：
10.1007/978-1-4939-9869-2_10
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发表时间：
2020-01-01
期刊：
影响因子：
--
通讯作者：
Buckle, Ashley M.
中科院分区：
文献类型：
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作者：
Chandler, Peter G.;Broendum, Sebastian S.;Buckle, Ashley M.
野生型蛋白质的稳定性往往是其在研究、工业和医学中实际应用的障碍。目的蛋白质的工程稳定性的途径很大程度上取决于可用的数据。在可以获得高分辨率结构数据的情况下，基于蛋白质化学基本原理的合理设计可以提高蛋白质稳定性。计算生物学的最新进展和非天然氨基酸的使用也为提高蛋白质稳定性提供了新的合理方法。同样，公共数据库中可用的序列和结构数据的爆炸性增长，加上免费计算工具的改进，产生了可用的系统发育方法。搜寻现代序列数据库可以识别靶蛋白的热稳定性同源物，并且可以使用可用的系统发育工具快速生成进化数据。从那些热稳定性同系物或祖先嫁接特征通过半理性方法提供了稳定性改进。此外，定向进化等分子技术在提供设计蛋白质方面显示出了巨大的前景。这些策略有据可查，并且分子生物学家最近可以使用这些策略，从而可以快速增强蛋白质稳定性。
The stability of wild-type proteins is often a hurdle to their practical use in research, industry, and medicine. The route to engineering stability of a protein of interest lies largely with the available data. Where high-resolution structural data is available, rational design, based on fundamental principles of protein chemistry, can improve protein stability. Recent advances in computational biology and the use of nonnatural amino acids have also provided novel rational methods for improving protein stability. Likewise, the explosion of sequence and structural data available in public databases, in combination with improvements in freely available computational tools, has produced accessible phylogenetic approaches. Trawling modern sequence databases can identify the thermostable homologs of a target protein, and evolutionary data can be quickly generated using available phylogenetic tools. Grafting features from those thermostable homologs or ancestors provides stability improvement through a semi-rational approach. Further, molecular techniques such as directed evolution have shown great promise in delivering designer proteins. These strategies are well documented and newly accessible to the molecular biologist, allowing for rapid enhancements of protein stability.