Molecular dynamics simulations of three-strand β-sheet folding

Hongwu Wang, Shen Shu Sung

Research output: Contribution to journalArticlepeer-review

43 Scopus citations


Traditionally, the empirical force field had great difficulties in simulating β-sheet folding. In the current study, we tested molecular dynamics simulations of β-sheet folding using a solvent-referenced potential. Three available β-sheet-forming synthetic peptides, TWIQNGSTKWYQNGSTKIYT, RGWSVQNGKYTNNGKTTEGR, and VFITS(D)PGKTYTEV(D)PGOKILQ, were simulated at their experimental temperatures. From extended initial conformations, all three peptides folded into β-sheet conformations. The calculated ratios of the β-structure from the 100 ns simulations were 26.5%, 17.8%, and 28.5%, respectively, for the three peptides. From different initial conformations, folding into β-sheets was also observed. With the same energy functions, the alanine-based peptide folded into helical conformations, demonstrating the sequence dependence of folding. During simulations, the β-sheet folding is usually initiated by the fast formation of turns. The three-strand compact structures with favorable inter-strand side-chain interactions occur prior to backbone hydrogen bonding. The conversion of the compact structure to β-sheet is slow, and the peptide spends most of the time in these two states. The attractive side-chain interaction is mainly due to the solvent effect, especially the hydrophobic interactions. Without this solvent effect, β-sheet did not form in the simulations. For the first two sequences, the simulations suggest that the experimentally observed structure may include an ensemble of β-sheet structures. For the (D)P-containing peptide, one β-sheet structure with type II' β-turns is much more stable than other structures.

Original languageEnglish (US)
Pages (from-to)1999-2009
Number of pages11
JournalJournal of the American Chemical Society
Issue number9
StatePublished - Mar 8 2000

All Science Journal Classification (ASJC) codes

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


Dive into the research topics of 'Molecular dynamics simulations of three-strand β-sheet folding'. Together they form a unique fingerprint.

Cite this