Abstract：
:Hybrid proteins or chimeras are generated by recombination of protein fragments. In the course of evolution, this mechanism has led to major diversification of protein folds and their functionalities. Similarly, protein engineers have taken advantage of this attractive strategy to build new proteins. Methods that use homologous recombination have been developed to (semi) randomly create chimeras from which the best can be selected. We wanted to recombine very divergent or even unrelated fragments, which is not possible with these methods. Consequently, based on the observation that nature evolves new proteins also through illegitimate recombination, we developed a strategy to design chimeras using protein fragments from different folds. For this approach, we employ detailed structure comparisons, and based on structural similarities, we choose the fragments used for recombination. Model building and minimization can be used to assess the design, and further optimization can be performed using established computational design methodologies. Here, we outline a general approach to rational protein chimera design based on our experience, and provide considerations for the selection of the fragments, the evaluation, and possible redesign of the constructs.
journal_name
Methods Enzymoljournal_title
Methods in enzymologyauthors
Rico JA,Höcker Bdoi
10.1016/B978-0-12-394292-0.00018-7subject
Has Abstractpub_date
2013-01-01 00:00:00pages
389-405eissn
0076-6879issn
1557-7988pii
B978-0-12-394292-0.00018-7journal_volume
523pub_type
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