De novo enzymes by computational design

被引:189
作者
Kries, Hajo [1 ]
Blomberg, Rebecca [2 ]
Hilvert, Donald [1 ]
机构
[1] ETH, Organ Chem Lab, CH-8093 Zurich, Switzerland
[2] Firmenich Co, Corp R&D Div, CH-1211 Geneva, Switzerland
关键词
PROTEIN DESIGN; COMPLEXES; CATALYSIS; QUANTUM; OPTIMIZATION; CHEMISTRY; THEOZYMES; ORIGINS;
D O I
10.1016/j.cbpa.2013.02.012
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
Computational enzyme design has emerged as a promising tool for generating made-to-order biocatalysts. In addition to improving the reliability of the design cycle, current efforts in this area are focusing on expanding the set of catalyzed reactions and investigating the structure and mechanism of individual designs. Although the activities of de novo enzymes are typically low, they can be significantly increased by directed evolution. Analysis of their evolutionary trajectories provides valuable feedback for the design algorithms and can enhance our understanding of natural protein evolution.
引用
收藏
页码:221 / 228
页数:8
相关论文
共 52 条
[1]   Advances in Quantum and Molecular Mechanical (QM/MM) Simulations for Organic and Enzymatic Reactions [J].
Acevedo, Orlando ;
Jorgensen, William L. .
ACCOUNTS OF CHEMICAL RESEARCH, 2010, 43 (01) :142-151
[2]   Catalytic Mechanism and Performance of Computationally Designed Enzymes for Kemp Elimination [J].
Alexandrova, Anastassia N. ;
Roethlisberger, Daniela ;
Baker, David ;
Jorgensen, William L. .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2008, 130 (47) :15907-15915
[3]   Robust design and optimization of retroaldol enzymes [J].
Althoff, Eric A. ;
Wang, Ling ;
Jiang, Lin ;
Giger, Lars ;
Lassila, Jonathan K. ;
Wang, Zhizhi ;
Smith, Matthew ;
Hari, Sanjay ;
Kast, Peter ;
Herschlag, Daniel ;
Hilvert, Donald ;
Baker, David .
PROTEIN SCIENCE, 2012, 21 (05) :717-726
[4]   An exciting but challenging road ahead for computational enzyme design [J].
Baker, David .
PROTEIN SCIENCE, 2010, 19 (10) :1817-1819
[5]   Enzyme-like proteins by computational design [J].
Bolon, DN ;
Mayo, SL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (25) :14274-14279
[6]   Protein design automation [J].
Dahiyat, BI ;
Mayo, SL .
PROTEIN SCIENCE, 1996, 5 (05) :895-903
[7]   Multistate approaches in computational protein design [J].
Davey, James A. ;
Chica, Roberto A. .
PROTEIN SCIENCE, 2012, 21 (09) :1241-1252
[8]   How similar are enzyme active site geometries derived from quantum mechanical theozymes to crystal structures of enzyme-inhibitor complexes? Implications for enzyme design [J].
Dechancie, Jason ;
Clemente, Fernando R. ;
Smith, Adam J. T. ;
Gunaydin, Hakan ;
Zhao, Yi-Lei ;
Zhang, Xiyun ;
Houk, N. .
PROTEIN SCIENCE, 2007, 16 (09) :1851-1866
[9]   Catalysis by a De Novo Zinc-Mediated Protein Interface: Implications for Natural Enzyme Evolution and Rational Enzyme Engineering [J].
Der, Bryan S. ;
Edwards, David R. ;
Kuhlman, Brian .
BIOCHEMISTRY, 2012, 51 (18) :3933-3940
[10]   Increased Diels-Alderase activity through backbone remodeling guided by Foldit players [J].
Eiben, Christopher B. ;
Siegel, Justin B. ;
Bale, Jacob B. ;
Cooper, Seth ;
Khatib, Firas ;
Shen, Betty W. ;
Players, Foldit ;
Stoddard, Barry L. ;
Popovic, Zoran ;
Baker, David .
NATURE BIOTECHNOLOGY, 2012, 30 (02) :190-192