Helix stability of oligoglycine, oligoalanine, and oligo-β-alanine dodecamers reflected by hydrogen-bond persistence

Chengyu Liu, Jay W. Ponder, Garland R. Marshall

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Helices are important structural/recognition elements in proteins and peptides. Stability and conformational differences between helices composed of α- and β-amino acids as scaffolds for mimicry of helix recognition has become a theme in medicinal chemistry. Furthermore, helices formed by β-amino acids are experimentally more stable than those formed by α-amino acids. This is paradoxical because the larger sizes of the hydrogen-bonding rings required by the extra methylene groups should lead to entropic destabilization. In this study, molecular dynamics simulations using the second-generation force field, AMOEBA (Ponder, J.W., et al., Current status of the AMOEBA polarizable force field. J Phys Chem B, 2010. 114(8): p. 2549-64.) explored the stability and hydrogen-bonding patterns of capped oligo-β-alanine, oligoalanine, and oligoglycine dodecamers in water. The MD simulations showed that oligo-β-alanine has strong acceptor+2 hydrogen bonds, but surprisingly did not contain a large content of 312-helical structures, possibly due to the sparse distribution of the 312-helical structure and other structures with acceptor+2 hydrogen bonds. On the other hand, despite its backbone flexibility, the β-alanine dodecamer had more stable and persistent <3.0 Å hydrogen bonds. Its structure was dominated more by multicentered hydrogen bonds than either oligoglycine or oligoalanine helices. The 31 (PII) helical structure, prevalent in oligoglycine and oligoalanine, does not appear to be stable in oligo-β-alanine indicating its competition with other structures (stacking structure as indicated by MD analyses). These differences are among the factors that shape helical structural preferences and the relative stabilities of these three oligopeptides.

Original languageEnglish
Pages (from-to)3043-3061
Number of pages19
JournalProteins: Structure, Function and Bioinformatics
Volume82
Issue number11
DOIs
StatePublished - Jan 1 2014

Keywords

  • AMOEBA force field
  • Beta amino acid
  • H-bond interchange
  • H-bond persistence
  • Helical conformation
  • Hydrogen bond
  • Polyalanine
  • Polyglycine
  • Replica-exchange MD

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