Computational design of heterochiral peptides against a helical target

Vikas Nanda, William F. DeGrado

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Polypeptides incorporating D-amino acids occasionally occur in nature and are an important class of pharmaceutical molecules. With the use of heterochiral Monte Carlo (HCMC), a method inspired by the de novo design of proteins, we develop peptide scaffolds for interacting with a molecular target, a left-handed α-helix. The HCMC approach concurrently seeks to optimize a peptide sequence, its internal conformation, and its docked conformation with a target surface. Several major classes of interactions are observed: (1) homochiral interactions between two αL helices, (2) heterochiral interactions between an αL and an αR helix, and (3) heterochiral interactions between the αL target and novel nonhelical structures. We explore the application of HCMC to simulating the preferential enantioselectivity of heterochiral complexes. Implications for biomimetic design in molecular recognition are discussed.

Original languageEnglish (US)
Pages (from-to)809-816
Number of pages8
JournalJournal of the American Chemical Society
Issue number3
StatePublished - Jan 25 2006

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry


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