Identification and insertion of 3-carbon bridges in protein disulfide bonds: A computational approach

Mire Zloh, S. Shaunak, S. Balan, S. Brocchini

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

More than 42,000 3D structures of proteins are available on the Internet. We have shown that the chemical insertion of a 3-carbon bridge across the native disulfide bond of a protein or peptide can enable the site-specific conjugation of PEG to the protein without a loss of its structure or function. For success, it is necessary to select an appropriate and accessible disulfide bond in the protein for this chemical modification. We describe how to use public protein databases and molecular modeling programs to select a protein rationally and to identify the optimum disulfide bond for experimental studies. Our computational approach can substantially reduce the time required for the laboratory-based chemical modification. Identification of solvent-accessible disulfides using published structural information takes approximately 2 h. Predicting the structural effects of the disulfide-based modification can take 3 weeks.
Original languageEnglish
Pages (from-to)1070-1083
Number of pages14
JournalNature Protocols
Volume2
Issue number5
DOIs
Publication statusPublished - 1 May 2007

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