AN ALGORITHM FOR PROTEIN ENGINEERING - SIMULATIONS OF RECURSIVE ENSEMBLE MUTAGENESIS

AN ALGORITHM FOR PROTEIN ENGINEERING - SIMULATIONS OF RECURSIVE ENSEMBLE MUTAGENESIS
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DOI:
10.1073/pnas.89.16.7811
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发表时间:
1992-08-15
影响因子:
11.1
通讯作者:
YOUVAN, DC
YOUVAN, DC
中科院分区:
综合性期刊1区
文献类型:
--
作者:
ARKIN, AP;YOUVAN, DC

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一种称为递归集合突变的蛋白质工程算法已经被开发出来,以产生不同群体的表型相关突变体,其成员的氨基酸序列不同。该方法采用一种反馈机制来控制连续的组合盒诱变。从部分随机的“野生型”DNA序列开始,对序列空间进行高度平行的搜索,以寻找符合实验者标准的肽。每次迭代都使用从前几轮获得的信息来更有效地搜索空间。该技术的仿真表明,在各种条件下,该算法可以快速产生符合特定标准的多种蛋白质。在实验模拟中,在递归集合突变过程中应用的遗传选择或筛选应该迫使突变集合进化到相关表型的目标簇。
An algorithm for protein engineering, termed recursive ensemble mutagenesis, has been developed to produce diverse populations of phenotypically related mutants whose members differ in amino acid sequence. This method uses a feedback mechanism to control successive rounds of combinatorial cassette mutagenesis. Starting from partially randomized "wild-type" DNA sequences, a highly parallel search of sequence space for peptides fitting an experimenter's criteria is performed. Each iteration uses information gained from the previous rounds to search the space more efficiently. Simulations of the technique indicate that, under a variety of conditions, the algorithm can rapidly produce a diverse population of proteins fitting specific criteria. In the experimental analog, genetic selection or screening applied during recursive ensemble mutagenesis should force the evolution of an ensemble of mutants to a targeted cluster of related phenotypes.