Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu, Taiwan.
Institute of Bioinformatics and Systems Biology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan.
BMC Bioinformatics. 2021 Oct 12;22(Suppl 10):494. doi: 10.1186/s12859-021-04403-1.
This work aims to help develop new protein engineering techniques based on a structural rearrangement phenomenon called circular permutation (CP), equivalent to connecting the native termini of a protein followed by creating new termini at another site. Although CP has been applied in many fields, its implementation is still costly because of inevitable trials and errors.
Here we present CirPred, a structure modeling and termini linker design method for circularly permuted proteins. Compared with state-of-the-art protein structure modeling methods, CirPred is the only one fully capable of both circularly-permuted modeling and traditional co-linear modeling. CirPred performs well when the permutant shares low sequence identity with the native protein and even when the permutant adopts a different conformation from the native protein because of three-dimensional (3D) domain swapping. Linker redesign experiments demonstrated that the linker design algorithm of CirPred achieved subangstrom accuracy.
The CirPred system is capable of (1) predicting the structure of circular permutants, (2) designing termini linkers, (3) performing traditional co-linear protein structure modeling, and (4) identifying the CP-induced occurrence of 3D domain swapping. This method is supposed helpful for broadening the application of CP, and its web server is available at http://10.life.nctu.edu.tw/CirPred/ and http://lo.life.nctu.edu.tw/CirPred/ .
本工作旨在帮助开发基于一种结构重排现象的新型蛋白质工程技术，这种现象称为环状排列（CP），相当于连接蛋白质的天然末端，然后在另一个位置创建新的末端。尽管 CP 已在许多领域得到应用，但由于不可避免的反复试验，其实施仍然成本高昂。
在这里，我们提出了 CirPred，这是一种用于环状排列蛋白质的结构建模和末端接头设计方法。与最先进的蛋白质结构建模方法相比，CirPred 是唯一一种既能进行环状排列建模又能进行传统共线性建模的方法。CirPred 在以下情况下表现良好：排列变体与天然蛋白质的序列同一性较低，甚至当排列变体由于三维（3D）结构域交换而采用与天然蛋白质不同的构象时。接头重新设计实验表明，CirPred 的接头设计算法达到了亚埃精度。
CirPred 系统能够（1）预测环状排列变体的结构，（2）设计末端接头，（3）进行传统的共线性蛋白质结构建模，以及（4）识别 CP 诱导的 3D 结构域交换的发生。这种方法有望拓宽 CP 的应用，其网络服务器可在 http://10.life.nctu.edu.tw/CirPred/ 和 http://lo.life.nctu.edu.tw/CirPred/ 访问。
