Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK.
Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK.
J Mol Biol. 2015 Jan 30;427(2):478-90. doi: 10.1016/j.jmb.2014.09.026. Epub 2014 Oct 14.
Protein solubility is often an essential requirement in biotechnological and biomedical applications. Great advances in understanding the principles that determine this specific property of proteins have been made during the past decade, in particular concerning the physicochemical characteristics of their constituent amino acids. By exploiting these advances, we present the CamSol method for the rational design of protein variants with enhanced solubility. The method works by performing a rapid computational screening of tens of thousand of mutations to identify those with the greatest impact on the solubility of the target protein while maintaining its native state and biological activity. The application to a single-domain antibody that targets the Alzheimer's Aβ peptide demonstrates that the method predicts with great accuracy solubility changes upon mutation, thus offering a cost-effective strategy to help the production of soluble proteins for academic and industrial purposes.
蛋白质溶解度通常是生物技术和生物医学应用的基本要求。在过去的十年中，人们在理解决定蛋白质这一特殊性质的原理方面取得了重大进展，特别是关于其组成氨基酸的物理化学特性。利用这些进展，我们提出了 CamSol 方法，用于合理设计具有增强溶解度的蛋白质变体。该方法通过对成千上万种突变进行快速计算筛选，来识别那些对目标蛋白质溶解度影响最大的突变，同时保持其天然状态和生物活性。该方法应用于靶向阿尔茨海默病 Aβ肽的单域抗体表明，该方法可以非常准确地预测突变后的溶解度变化，从而为学术和工业目的提供一种具有成本效益的策略，帮助生产可溶性蛋白质。
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