Identification and Analysis of Natural Building Blocks for Evolution-Guided Fragment-Based Protein Design

被引:25
作者
Ferruz, Noelia [1 ]
Lobos, Francisco [1 ,2 ]
Lemm, Dominik [1 ]
Toledo-Patino, Saacnicteh [1 ,2 ]
Farias-Rico, Jose Arcadio [2 ]
Schmidt, Steffen [2 ,3 ]
Hoecker, Birte [1 ,2 ]
机构
[1] Univ Bayreuth, Dept Biochem, Bayreuth, Germany
[2] Max Planck Inst Dev Biol, Tubingen, Germany
[3] Univ Bayreuth, Computat Biochem, Bayreuth, Germany
基金
欧洲研究理事会;
关键词
protein design; evolution; protein recombination; protein fragments; LIGAND-BINDING; COMPUTATIONAL DESIGN; CRYSTAL-STRUCTURE; DOMAIN; ANGSTROM; ENZYME; HOMOLOGY; OPTIMIZATION; DATABASE; SYMMETRY;
D O I
10.1016/j.jmb.2020.04.013
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Natural evolution has generated an impressively diverse protein universe via duplication and recombination from a set of protein fragments that served as building blocks. The application of these concepts to the design of new proteins using subdomain-sized fragments from different folds has proven to be experimentally successful. To better understand how evolution has shaped our protein universe, we performed an all-against-all comparison of protein domains representing all naturally existing folds and identified conserved homologous protein fragments. Overall, we found more than 1000 protein fragments of various lengths among different folds through similarity network analysis. These fragments are present in very different protein environments and represent versatile building blocks for protein design. These data are available in our web server called F(old P)uzzle (fuzzle.uni-bayreuth.de), which allows to individually filter the dataset and create customized networks for folds of interest. We believe that our results serve as an invaluable resource for structural and evolutionary biologists and as raw material for the design of custom-made proteins. (C) 2020 The Author(s). Published by Elsevier Ltd.
引用
收藏
页码:3898 / 3914
页数:17
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