Folding of a helix at room temperature is critically aided by electrostatic polarization of intraprotein hydrogen bonds

Li L. Duan, Ye Mei, Dawei Zhang, Qing G. Zhang, John Zhang

Research output: Contribution to journalArticle

Abstract

We report direct folding of a 17-residue helix protein (pdb:2I9M) by standard molecular dynamics simulation (single trajectory) at room temperature with implicit solvent. Starting from a fully extended structure, 2I9M successfully folds into the native conformation within 16 ns using adaptive hydrogen bond-specific charges to take into account the electrostatic polarization effect. Cluster analysis shows that conformations in the native state cluster have the highest population (78.4%) among all sampled conformations. Folding snapshots and the secondary structure analysis demonstrate that the folding of 2I9M begins at terminals and progresses toward the center. A plot of the free energy landscape indicates that there is no significant free energy barrier during folding, which explains the observed fast folding speed. For comparison, exactly the same molecular dynamics simulation but carried out under existing AMBER charges failed to fold 2I9M into native-like structures. The current study demonstrates that electrostatic polarization of intraprotein hydrogen bonding, which stabilizes the helix, is critical to the successful folding of 2I9m.

Original languageEnglish (US)
Pages (from-to)11159-11164
Number of pages6
JournalJournal of the American Chemical Society
Volume132
Issue number32
DOIs
StatePublished - Aug 18 2010

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Molecular Dynamics Simulation
Static Electricity
Conformations
Hydrogen
Electrostatics
Hydrogen bonds
Polarization
Free energy
Temperature
Molecular dynamics
Hydrogen Bonding
Cluster Analysis
Energy barriers
Computer simulation
Cluster analysis
Trajectories
Population
Proteins

ASJC Scopus subject areas

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

Cite this

Folding of a helix at room temperature is critically aided by electrostatic polarization of intraprotein hydrogen bonds. / Duan, Li L.; Mei, Ye; Zhang, Dawei; Zhang, Qing G.; Zhang, John.

In: Journal of the American Chemical Society, Vol. 132, No. 32, 18.08.2010, p. 11159-11164.

Research output: Contribution to journalArticle

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N2 - We report direct folding of a 17-residue helix protein (pdb:2I9M) by standard molecular dynamics simulation (single trajectory) at room temperature with implicit solvent. Starting from a fully extended structure, 2I9M successfully folds into the native conformation within 16 ns using adaptive hydrogen bond-specific charges to take into account the electrostatic polarization effect. Cluster analysis shows that conformations in the native state cluster have the highest population (78.4%) among all sampled conformations. Folding snapshots and the secondary structure analysis demonstrate that the folding of 2I9M begins at terminals and progresses toward the center. A plot of the free energy landscape indicates that there is no significant free energy barrier during folding, which explains the observed fast folding speed. For comparison, exactly the same molecular dynamics simulation but carried out under existing AMBER charges failed to fold 2I9M into native-like structures. The current study demonstrates that electrostatic polarization of intraprotein hydrogen bonding, which stabilizes the helix, is critical to the successful folding of 2I9m.

AB - We report direct folding of a 17-residue helix protein (pdb:2I9M) by standard molecular dynamics simulation (single trajectory) at room temperature with implicit solvent. Starting from a fully extended structure, 2I9M successfully folds into the native conformation within 16 ns using adaptive hydrogen bond-specific charges to take into account the electrostatic polarization effect. Cluster analysis shows that conformations in the native state cluster have the highest population (78.4%) among all sampled conformations. Folding snapshots and the secondary structure analysis demonstrate that the folding of 2I9M begins at terminals and progresses toward the center. A plot of the free energy landscape indicates that there is no significant free energy barrier during folding, which explains the observed fast folding speed. For comparison, exactly the same molecular dynamics simulation but carried out under existing AMBER charges failed to fold 2I9M into native-like structures. The current study demonstrates that electrostatic polarization of intraprotein hydrogen bonding, which stabilizes the helix, is critical to the successful folding of 2I9m.

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