Protein design by directed evolution

被引:275
作者
Jaeckel, Christian [1 ]
Kast, Peter [1 ]
Hilvert, Donald [1 ]
机构
[1] ETH, Organ Chem Lab, CH-8093 Zurich, Switzerland
关键词
molecular diversity; random mutagenesis; screening; selection; enzymes; computational design;
D O I
10.1146/annurev.biophys.37.032807.125832
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
While nature evolved polypeptides over billions of years, protein design by evolutionary mimicry is progressing at a far more rapid pace. The mutation, selection, and amplification steps of the evolutionary cycle may be imitated in the laboratory using existing proteins, or molecules created de novo from random sequence space, as starting templates. However, the astronomically large number of possible polypeptide sequences remains an obstacle to identifying and isolating functionally interesting variants. Intelligently designed libraries and improved search techniques are consequently important for future advances. In this regard, combining experimental and computational methods holds particular promise for the creation of tailored protein receptors and catalysts for tasks unimagined by nature.
引用
收藏
页码:153 / 173
页数:21
相关论文
共 90 条
[31]   PROTEIN DESIGN BY BINARY PATTERNING OF POLAR AND NONPOLAR AMINO-ACIDS [J].
KAMTEKAR, S ;
SCHIFFER, JM ;
XIONG, HY ;
BABIK, JM ;
HECHT, MH .
SCIENCE, 1993, 262 (5140) :1680-1685
[32]   De novo design of catalytic proteins [J].
Kaplan, J ;
DeGrado, WF .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (32) :11566-11570
[33]   Exploring the active site of chorismate mutase by combinatorial mutagenesis and selection: The importance of electrostatic catalysis [J].
Kast, P ;
AsifUllah, M ;
Jiang, N ;
Hilvert, D .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (10) :5043-5048
[34]   Functional proteins from a random-sequence library [J].
Keefe, AD ;
Szostak, JW .
NATURE, 2001, 410 (6829) :715-718
[35]   Filamentous phage display in the new millennium [J].
Kehoe, JW ;
Kay, BK .
CHEMICAL REVIEWS, 2005, 105 (11) :4056-4072
[36]   Metabolic engineering of a genetic selection system with tunable stringency [J].
Kleeb, Andreas C. ;
Edalat, Maryam Hansson ;
Gamper, Marianne ;
Haugstetter, Johannes ;
Giger, Lars ;
Neuenschwander, Martin ;
Kast, Peter ;
Hilvert, Donald .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (35) :13907-13912
[37]   Design of a novel globular protein fold with atomic-level accuracy [J].
Kuhlman, B ;
Dantas, G ;
Ireton, GC ;
Varani, G ;
Stoddard, BL ;
Baker, D .
SCIENCE, 2003, 302 (5649) :1364-1368
[38]   Mechanistic insights into the isochorismate pyruvate lyase activity of the catalytically promiscuous PchB from combinatorial mutagenesis and selection [J].
Künzler, D ;
Sasso, S ;
Gamper, M ;
Hilvert, D ;
Kast, P .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (38) :32827-32834
[39]  
Lin HN, 2002, ANGEW CHEM INT EDIT, V41, P4403
[40]   A novel ADP- and zinc-binding fold from function-directed in vitro evolution [J].
Lo Surdo, P ;
Walsh, MA ;
Sollazzo, M .
NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2004, 11 (04) :382-383