Incorporation of Noncanonical Amino Acids into Rosetta and Use in Computational Protein-Peptide Interface Design

Department of Biology, Center for Genomics and Systems Biology, New York University, New York, New York, United States of America.
PLoS ONE (Impact Factor: 3.23). 03/2012; 7(3):e32637. DOI: 10.1371/journal.pone.0032637
Source: PubMed


Noncanonical amino acids (NCAAs) can be used in a variety of protein design contexts. For example, they can be used in place of the canonical amino acids (CAAs) to improve the biophysical properties of peptides that target protein interfaces. We describe the incorporation of 114 NCAAs into the protein-modeling suite Rosetta. We describe our methods for building backbone dependent rotamer libraries and the parameterization and construction of a scoring function that can be used to score NCAA containing peptides and proteins. We validate these additions to Rosetta and our NCAA-rotamer libraries by showing that we can improve the binding of a calpastatin derived peptides to calpain-1 by substituting NCAAs for native amino acids using Rosetta. Rosetta (executables and source), auxiliary scripts and code, and documentation can be found at (

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Available from: Richard Bonneau, Oct 08, 2015
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    • "protocol that samples side chain x angles of an amino acid for w=y combinations of backbone angles . Side chain conforma - tion samples are clustered and an energy score is calculated for each cluster . The energy is then converted into a probability that serves as an entry in the ResidueType ' s rotamer library . The full protocol is discussed by Renfrew et al . 2012 , along with a protocol capture describing how to run the code [ 39 ] . It should be noted that it is unnecessary to create new rotamer libraries if it is believed there is a suitable available rotamer library . For example in the case of HBS helices the backbone is similar to the peptide backbone ( identical at most positions ) and thu"
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