Extended Concerted Rotation Technique Enhances the Sampling Efficiency of the Computational Peptide-Design Algorithm

Xingqing Xiao, Yiming Wang, Joshua N. Leonard, Carol K. Hall*

*Corresponding author for this work

Research output: Contribution to journalArticle

2 Scopus citations


To enhance the sampling efficiency of our computational peptide-design algorithm in conformational space, the concerted rotation (CONROT) technique is extended to enable larger conformational perturbations of peptide chains. This allows us to make relatively large peptide conformation changes during the process of designing peptide sequences to bind with high affinity to a specific target. Searches conducted using the new algorithm identified six potential λ N(2-22) peptide variants, called B1-B6, which bind to boxB RNA with high affinity. The results of explicit-solvent atomistic molecular dynamics simulations revealed that four of the evolved peptides, viz. B1, B2, B3, and B5, are excellent candidate binders to the target boxB RNA as they have lower binding free energies than the original λ N(2-22) peptide. Three of the four peptides, B2, B3, and B5, result from searches that contain both sequence and conformation changes, indicating that adding backbone motif changes to the peptide-design algorithm improves its performance considerably.

Original languageEnglish (US)
Pages (from-to)5709-5720
Number of pages12
JournalJournal of Chemical Theory and Computation
Issue number11
Publication statusPublished - Nov 14 2017


ASJC Scopus subject areas

  • Computer Science Applications
  • Physical and Theoretical Chemistry

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