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通过定向进化进行蛋白质设计。

Protein design by directed evolution.

作者信息

Jäckel Christian, Kast Peter, Hilvert Donald

机构信息

Laboratory of Organic Chemistry, ETH Zurich, CH-8093 Zurich, Switzerland.

出版信息

Annu Rev Biophys. 2008;37:153-73. doi: 10.1146/annurev.biophys.37.032807.125832.

Abstract

While nature evolved polypeptides over billions of years, protein design by evolutionary mimicry is progressing at a far more rapid pace. The mutation, selection, and amplification steps of the evolutionary cycle may be imitated in the laboratory using existing proteins, or molecules created de novo from random sequence space, as starting templates. However, the astronomically large number of possible polypeptide sequences remains an obstacle to identifying and isolating functionally interesting variants. Intelligently designed libraries and improved search techniques are consequently important for future advances. In this regard, combining experimental and computational methods holds particular promise for the creation of tailored protein receptors and catalysts for tasks unimagined by nature.

摘要

虽然大自然历经数十亿年进化出了多肽,但通过进化模拟进行的蛋白质设计正以快得多的速度发展。进化循环中的突变、选择和扩增步骤可以在实验室中使用现有蛋白质或从随机序列空间中从头创建的分子作为起始模板来模仿。然而,数量极其庞大的可能多肽序列仍然是识别和分离具有功能意义的变体的障碍。因此,智能设计的文库和改进的搜索技术对于未来的进展至关重要。在这方面,将实验方法和计算方法相结合对于创建自然界未曾设想过的任务的定制蛋白质受体和催化剂具有特别的前景。

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