Electronic polarization stabilizes tertiary structure prediction of HP-36

Li L. Duan, Tong Zhu, Qing G. Zhang, Bo Tang, John Zhang

Research output: Contribution to journalArticle

Abstract

Molecular dynamic (MD) simulations with both implicit and explicit solvent models have been carried out to study the folding dynamics of HP-36 protein. Starting from the extended conformation, the secondary structure of all three helices in HP-36 was formed in about 50 ns and remained stable in the remaining simulation. However, the formation of the tertiary structure was difficult. Although some intermediates were close to the native structure, the overall conformation was not stable. Further analysis revealed that the large structure fluctuation of loop and hydrophobic core regions was devoted mostly to the instability of the structure during MD simulation. The backbone root-mean-square deviation (RMSD) of the loop and hydrophobic core regions showed strong correlation with the backbone RMSD of the whole protein. The free energy landscape indicated that the distribution of main chain torsions in loop and turn regions was far away from the native state. Starting from an intermediate structure extracted from the initial AMBER simulation, HP-36 was found to generally fold to the native state under the dynamically adjusted polarized protein-specific charge (DPPC) simulation, while the peptide did not fold into the native structure when AMBER force filed was used. The two best folded structures were extracted and taken into further simulations in water employing AMBER03 charge and DPPC for 25 ns. Result showed that introducing polarization effect into interacting potential could stabilize the near-native protein structure.

Original languageEnglish (US)
Article number2195
JournalJournal of Molecular Modeling
Volume20
Issue number4
DOIs
StatePublished - 2014

Fingerprint

Polarization
Proteins
proteins
polarization
predictions
electronics
simulation
Conformations
Molecular dynamics
molecular dynamics
deviation
Computer simulation
Torsional stress
Peptides
Free energy
helices
folding
torsion
peptides
villin headpiece subdomain peptide

Keywords

  • Molecular dynamics
  • Polarization effect
  • Protein folding
  • Solvent model

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Computer Science Applications
  • Computational Theory and Mathematics
  • Catalysis
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Electronic polarization stabilizes tertiary structure prediction of HP-36. / Duan, Li L.; Zhu, Tong; Zhang, Qing G.; Tang, Bo; Zhang, John.

In: Journal of Molecular Modeling, Vol. 20, No. 4, 2195, 2014.

Research output: Contribution to journalArticle

Duan, Li L. ; Zhu, Tong ; Zhang, Qing G. ; Tang, Bo ; Zhang, John. / Electronic polarization stabilizes tertiary structure prediction of HP-36. In: Journal of Molecular Modeling. 2014 ; Vol. 20, No. 4.
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AB - Molecular dynamic (MD) simulations with both implicit and explicit solvent models have been carried out to study the folding dynamics of HP-36 protein. Starting from the extended conformation, the secondary structure of all three helices in HP-36 was formed in about 50 ns and remained stable in the remaining simulation. However, the formation of the tertiary structure was difficult. Although some intermediates were close to the native structure, the overall conformation was not stable. Further analysis revealed that the large structure fluctuation of loop and hydrophobic core regions was devoted mostly to the instability of the structure during MD simulation. The backbone root-mean-square deviation (RMSD) of the loop and hydrophobic core regions showed strong correlation with the backbone RMSD of the whole protein. The free energy landscape indicated that the distribution of main chain torsions in loop and turn regions was far away from the native state. Starting from an intermediate structure extracted from the initial AMBER simulation, HP-36 was found to generally fold to the native state under the dynamically adjusted polarized protein-specific charge (DPPC) simulation, while the peptide did not fold into the native structure when AMBER force filed was used. The two best folded structures were extracted and taken into further simulations in water employing AMBER03 charge and DPPC for 25 ns. Result showed that introducing polarization effect into interacting potential could stabilize the near-native protein structure.

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