Computational Design of the Sequence and Structure of a Protein-Binding Peptide

Journal Article · Fri Aug 10 00:00:00 EDT 2012 · J. Am. Chem. Soc.

DOI:https://doi.org/10.1021/ja110296z· OSTI ID:1040889

Sammond, Deanne W; Bosch, Dustin E; Butterfoss, Glenn L; Purbeck, Carrie; Machius, Mischa; Siderovski, David P; Kuhlman, Brian ^[1]

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1. UNC

The de novo design of protein-binding peptides is challenging because it requires the identification of both a sequence and a backbone conformation favorable for binding. We used a computational strategy that iterates between structure and sequence optimization to redesign the C-terminal portion of the RGS14 GoLoco motif peptide so that it adopts a new conformation when bound to G{alpha}{sub i1}. An X-ray crystal structure of the redesigned complex closely matches the computational model, with a backbone root-mean-square deviation of 1.1 {angstrom}.

• Research Organization: Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
• Sponsoring Organization: OTHERNIH
• OSTI ID: 1040889
• Journal Information: J. Am. Chem. Soc., Vol. 133, Issue (12) ; 03, 2011; ISSN 0002-7863
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

37 INORGANIC
ORGANIC
PHYSICAL AND ANALYTICAL CHEMISTRY
CRYSTAL STRUCTURE
DESIGN
OPTIMIZATION
PEPTIDES