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Published February 2006 | public
Journal Article

A search algorithm for fixed-composition protein design


We present a computational protein design algorithm for finding low-energy sequences of fixed amino acid composition. The search algorithms used in protein design typically do not restrict amino acid composition. However, the random energy model of Shakhnovich suggests that the use of fixed-composition sequences may circumvent defects in the modeling of the denatured state. Our algorithm, FC_FASTER, links fixed-composition versions of Monte Carlo and the FASTER algorithm. As proof of principle, FC_FASTER was tested on an experimentally validated, full-sequence design of the β1 domain of protein G. For the wild-type composition, FC_FASTER found a lower energy sequence than the experimentally validated sequence. Also, for a different composition, FC_FASTER found the hypothetical lowest-energy sequence in 14 out of 32 trials.

Additional Information

© 2005 Wiley Periodicals, Inc. Article first published online: 27 Dec. 2005. We are grateful to Ben Allen for help with FASTER and to Oscar Alvizo for sharing his results on G1 prior to publication and for providing the test file. We also thank them and Marie Ary, Po-Ssu Huang, and Christina Vizcarra for assistance with the manuscript.

Additional details

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