Solubis: optimize your protein
Solubis: optimize your protein
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DOI：
10.1093/bioinformatics/btv162
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发表时间：
2015-08-01
期刊：
影响因子：
5.8
通讯作者：
Rousseau, Frederic
中科院分区：
文献类型：
--
作者：
De Baets, Greet;Van Durme, Joost;Rousseau, Frederic
动机：蛋白质聚集与许多蛋白质错误折叠疾病有关，是治疗性蛋白质的主要关注点。聚集是由蛋白质氨基酸序列中存在聚集倾向区域 (APR) 引起的。 APR 的聚集倾向越低，并且它们受到蛋白质折叠结构内的天然相互作用的保护越好，就越能防止聚集。因此，APR 在天然结构中的局部热力学稳定性及其内在聚集倾向都是需要优化以防止蛋白质聚集的关键参数。结果：此处介绍的 Solubis 方法可自动执行仔细选择点突变的过程，最大限度地减少内在聚集倾向，同时提高局部蛋白质稳定性。
Motivation: Protein aggregation is associated with a number of protein misfolding diseases and is a major concern for therapeutic proteins. Aggregation is caused by the presence of aggregation-prone regions (APRs) in the amino acid sequence of the protein. The lower the aggregation propensity of APRs and the better they are protected by native interactions within the folded structure of the protein, the more aggregation is prevented. Therefore, both the local thermodynamic stability of APRs in the native structure and their intrinsic aggregation propensity are a key parameter that needs to be optimized to prevent protein aggregation.Results: The Solubis method presented here automates the process of carefully selecting point mutations that minimize the intrinsic aggregation propensity while improving local protein stability.