Journal
BIOMOLECULAR ENGINEERING
Volume 22, Issue 4, Pages 105-112Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bioeng.2005.06.001
Keywords
directed evolution; library; molecular diversity; random mutagenesis; redundancy
Funding
- NIAID NIH HHS [1 R21AI054602-01] Funding Source: Medline
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In the last decade, directed evolution has become a routine approach for engineering proteins with novel or altered properties. Concurrently, a trend away from purely 'blind' randomization strategies and towards more 'semi-rational' approaches has also become apparent. In this review, we discuss ways in which structural information and predictive computational tools are playing an increasingly important role in guiding the design of randomized libraries: web servers such as ConSurf-HSSP and SCHEMA allow the prediction of sites to target for producing functional variants, while algorithms such as GLUE, PEDEL and DRIVeR are useful for estimating library completeness and diversity. In addition, we review recent methodological developments that facilitate the construction of unbiased libraries, which are inherently more diverse than biased libraries and therefore more likely to yield improved variants. (C) 2005 Elsevier B.V. All rights reserved.
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