De novo design of a non-local β-sheet protein with high stability and accuracy.
De novo design of a non-local β-sheet protein with high stability and accuracy.
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DOI：
10.1038/s41594-018-0141-6
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发表时间：
2018-11
影响因子：
16.8
通讯作者：
Baker D
中科院分区：
文献类型：
--
作者：
Marcos E;Chidyausiku TM;McShan AC;Evangelidis T;Nerli S;Carter L;Nivón LG;Davis A;Oberdorfer G;Tripsianes K;Sgourakis NG;Baker D
β折叠蛋白在生物学中具有重要的功能，因此是计算蛋白质设计的有吸引力的支架。尽管有这种潜力，但由于其非局部性质和暴露的β链边缘聚集的趋势，从第一原理重新设计所有β折叠蛋白远远落后于所有α或混合αβ结构域的设计。通过研究连接未配对β链的环（β-拱），我们确定了环几何形状、侧链方向性和β链长度之间的一系列结构关系，这些关系源于氢键和对规则β-折叠结构的堆积约束。我们使用这些规则从头设计具有由8个反平行β-链形成的双链β-螺旋的卷曲结构。超热稳定设计的核磁共振结构与计算模型密切匹配，证明了对β-折叠结构和环几何形状的精确控制。我们的研究结果为设计广泛的非局部β折叠蛋白质结构打开了大门。
β-sheet proteins carry out critical functions in biology, and hence are attractive scaffolds for computational protein design. Despite this potential, de novo design of all β-sheet proteins from first principles lags far behind the design of all-α or mixed αβ domains due to their non-local nature and tendency of exposed β-strand edges to aggregate. Through study of loops connecting unpaired β-strands (β-arches), we have identified a series of structural relationships between loop geometry, sidechain directionality and β-strand length that arise from hydrogen bonding and packing constraints on regular β-sheet structures. We use these rules to de novo design jelly-roll structures with double-stranded β-helices formed by 8 antiparallel β-strands. The nuclear magnetic resonance structure of a hyperthermostable design closely matched the computational model, demonstrating accurate control over the β-sheet structure and loop geometry. Our results open the door to the design of a broad range of non-local β-sheet protein structures.
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影响因子：
64.8
作者：
Bhardwaj, Gaurav;Mulligan, Vikram Khipple;Bahl, Christopher D.;Gilmore, Jason M.;Harvey, Peta J.;Cheneval, Olivier;Buchko, Garry W.;Pulavarti, Surya V. S. R. K.;Kaas, Quentin;Eletsky, Alexander;Huang, Po-Ssu;Johnsen, William A.;Greisen, Per Jr;Rocklin, Gabriel J.;Song, Yifan;Linsky, Thomas W.;Watkins, Andrew;Rettie, Stephen A.;Xu, Xianzhong;Carter, Lauren P.;Bonneau, Richard;Olson, James M.;Coutsias, Evangelos;Correnti, Colin E.;Szyperski, Thomas;Craik, David J.;Baker, David
通讯作者：
Baker, David
影响因子：
1.9
作者：
Costantini S;Colonna G;Facchiano AM
通讯作者：
Facchiano AM
DOI：
10.1073/pnas.97.19.10383
发表时间：
2000-09-12
影响因子：
11.1
作者：
Kuhlman, B;Baker, D
通讯作者：
Baker, D
DOI：
10.1107/s0907444909042073
发表时间：
2010-01
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Chen VB;Arendall WB 3rd;Headd JJ;Keedy DA;Immormino RM;Kapral GJ;Murray LW;Richardson JS;Richardson DC
通讯作者：
Richardson DC
影响因子：
5.7
作者：
Hu, Xiaozhen;Wang, Huanchen;Kuhlman, Brian
通讯作者：
Kuhlman, Brian