针对目标基板的小型伊米因降解酶面板的基于结构的设计
Yuqi Yu1,2, Arnau Rué Casamajo1, William Finnigan1
1Department of Chemistry, The University of Manchester, Manchester Institute of Biotechnology, 131 Princess Street, Manchester M1 7DN, U.K.
概括
识别用于药物开发的新酶是具有挑战性的. IREDFisher是一种计算工具,可以快速选胺基还原酶 (IRED),显著减少实验室选时间和生物催化剂发现成本.
科学领域:
- 生物催化和酶工程 生物催化和酶工程
- 计算化学和化学信息学
- 制药科学 制药科学
背景情况:
- 生物催化对于制药的发现,开发和制造至关重要.
- 识别适合特定化学转换的酶往往需要广泛的选.
- 现有的酶发现方法资源密集,需要大量的时间和实验室工作.
研究的目的:
- 开发和验证基于结构的计算工作流程,IREDFisher,用于优先考虑酶序列.
- 减少在生物催化剂发现中需要广泛的实验室查的需要.
- 为了加快对药物应用中的 imine 减少酶 (IRED) 的识别.
主要方法:
- 开发了一个计算工作流 (IREDFisher) 以基于基质预测活动来得分蛋白质序列.
- 使用imine减少酶 (IREDs) 作为模型酶类来展示工作流的应用.
- 使用已发布的数据验证了工作流,并通过计算选了1400个IRED序列以检测还原性氨基化反应.
主要成果:
- 通过识别排名最高的序列,IREDFisher成功地检索出最好的酶,并增加了命中率.
- 计算查发现了高度活跃的IRED,只需要20个体外试验.
- 该工作流显示出高效率,在90分钟内排列了85个序列,并利用了591个IRED序列的已建立数据库.
结论:
- IREDFisher显著加快了用于合成和定向进化的imine减少酶 (IREDs) 的发现.
- 计算方法最大限度地减少了生物催化剂选中的时间和资源支出.
- 该工作流可通过修改其得分功能来适应其他酶家族,为更广泛的应用铺平了道路.
相关概念视频
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