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    Science. 2011 Oct 21;334(6054):373-6.

    Computation-guided backbone grafting of a discontinuous motif onto a protein scaffold.

    Source

    Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.

    Abstract

    The manipulation of protein backbone structure to control interaction and function is a challenge for protein engineering. We integrated computational design with experimental selection for grafting the backbone and side chains of a two-segment HIV gp120 epitope, targeted by the cross-neutralizing antibody b12, onto an unrelated scaffold protein. The final scaffolds bound b12 with high specificity and with affinity similar to that of gp120, and crystallographic analysis of a scaffold bound to b12 revealed high structural mimicry of the gp120-b12 complex structure. The method can be generalized to design other functional proteins through backbone grafting.

    PMID:
    22021856
    [PubMed - indexed for MEDLINE]

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