美国加州大学旧金山分校Tanja Kortemme、Xingjie Pan等研究人员合作通过计算设计，实现蛋白质几何结构的空间拓展。相关论文于2020年8月28日发表在《科学》杂志上。

Title: Expanding the space of protein geometries by computational design of de novo fold families

Author: Xingjie Pan, Michael C. Thompson, Yang Zhang, Lin Liu, James S. Fraser, Mark J. S. Kelly, Tanja Kortemme

Issue&Volume: 2020/08/28

Abstract: Naturally occurring proteins vary the precise geometries of structural elements to create distinct shapes optimal for function. We present a computational design method, loop-helix-loop unit combinatorial sampling (LUCS), that mimics nature’s ability to create families of proteins with the same overall fold but precisely tunable geometries. Through near-exhaustive sampling of loop-helix-loop elements, LUCS generates highly diverse geometries encompassing those found in nature but also surpassing known structure space. Biophysical characterization showed that 17 (38%) of 45 tested LUCS designs encompassing two different structural topologies were well folded, including 16 with designed non-native geometries. Four experimentally solved structures closely matched the designs. LUCS greatly expands the designable structure space and offers a new paradigm for designing proteins with tunable geometries that may be customizable for novel functions.

DOI: 10.1126/science.abc0881

Source: https://science.sciencemag.org/content/369/6507/1132