巴塞罗那科学技术学院的Ben Lehner和Jörn M. Schmiedel成功提出了一种深度诱变法，可用于测定蛋白质的结构。相关论文于2019年7月发表于国际学术期刊《自然—遗传学》上。

研究小组提出一种新方法，只需要测量分子的突变活性，便可以确定生物大分子的高分辨骨架结构。这种结构确定的遗传方法依赖于突变之间遗传相互作用（上位性）的量化以及直接间接相互作用的差异性。这为结构确定提供了另一种实验策略，具有揭示功能和体内结构的潜力。

研究人员表示，由于结构与功能的密切关系，确定大分子的三维结构是生物学研究的主要目标; 然而，成千上万的蛋白质结构域仍然有未知的结构。蛋白质结构的测定通常采用物理技术，例如X射线晶体学、核磁共振波谱学和冷冻电子显微镜技术。

附：英文原文

Title: Determining protein structures using deep mutagenesis

Author: Jrn M. Schmiedel, Ben Lehner

Issue&Volume: Volume 51 Issue 7, July 2019

Abstract: Determining the three-dimensional structures of macromolecules is a major goal of biological research, because of the close relationship between structure and function; however, thousands of protein domains still have unknown structures. Structure determination usually relies on physical techniques including X-ray crystallography, NMR spectroscopy and cryo-electron microscopy. Here we present a method that allows the high-resolution three-dimensional backbone structure of a biological macromolecule to be determined only from measurements of the activity of mutant variants of the molecule. This genetic approach to structure determination relies on the quantification of genetic interactions (epistasis) between mutations and the discrimination of direct from indirect interactions. This provides an alternative experimental strategy for structure determination, with the potential to reveal functional and in vivo structures.

DOI: 10.1038/s41588-019-0431-x

Source: https://www.nature.com/articles/s41588-019-0431-x