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Published July 2002 | public
Journal Article

Protein building blocks preserved by recombination


Borrowing concepts from the schema theory of genetic algorithms, we have developed a computational algorithm to identify the fragments of proteins, or schemas, that can be recombined without disturbing the integrity of the three-dimensional structure. When recombination leaves these schemas undisturbed, the hybrid proteins are more likely to be folded and functional. Crossovers found by screening libraries of several randomly shuffled proteins for functional hybrids strongly correlate with those predicted by this approach. Experimental results from the construction of hybrids of two beta-lactamases that share 40% amino acid identity demonstrate a threshold in the amount of schema disruption that the hybrid protein can tolerate. To the extent that introns function to promote recombination within proteins, natural selection would serve to bias their locations to schema boundaries.

Additional Information

© 2002 Nature Publishing Group. Published online: 3 June 2002; Corrected online: 10 June 2002. C.A.V. is supported by a National Science Foundation graduate research fellowship and the California Institute of Technology Initiative in Computational Molecular Biology, a Burroughs Wellcome funded program for science at the interface. Z.G.W. acknowledges the support by the W.M. Keck Foundation. S.L.M. is supported by the Howard Hughes Medical Institute, the Ralph M. Parsons Foundation and an IBM Shared University Research Grant. The PSE-4 gene and the PMON vector were provided by R.C. Levesque (Université Laval, Québec, Canada).

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