Molecular dynamics analysis of the conformations of a β-hairpin miniprotein

Marcus P D Hatfield, Richard F. Murphy, Sándor Lovas

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Molecular dynamics simulations of a β-hairpin miniprotein, CLN025, were performed to examine the conformational stability of the peptide in H 2O at 278, 300, 333, and 363 K, as well as in TFE, MeOH, and DMSO at 300 K. CLN025 is a variant of the Chignolin miniprotein, in which the terminal Gly residues of Chignolin are replaced with Tyr residues, which leads to a 29.7 K increase in melting temperature. The energy of the intramolecular interactions was calculated using DFT quantum chemical calculations at the BHandHLYP/cc-pVTZ level of theory. CLN025 maintained a β-hairpin conformation in all environments. The β-hairpin is stabilized by hydrogen bonds, an electrostatic interaction between the charged termini of the peptide, and weakly polar interactions. The interaction between the backbones of the N and C-terminal strands accounts for -97.32 to -120.87 kcal mol-1 of the stabilization energy. The energies of the CH-π interactions between Tyr2 and Pro4 were between -1.80 and -8.9 kcal mol-1, and the energy of the Tyr2-Trp9 Ar-Ar interaction was between -0.43 and -8.11 kcal mol-1. Increasing temperature caused the Tyr2-Pro4 CH-π and the Tyr2-Trp9 and Tyr2-Tyr10 Ar-Ar interactions to become less favorable, but the Tyr1-Trp9 interaction became more favorable and played an important role in stabilizing the β-hairpin of CLN025 that resulted in the increased melting temperature. Weakly polar interactions play an important role in the structure and stability of CLN025 and other proteins.

Original languageEnglish
Pages (from-to)3028-3037
Number of pages10
JournalJournal of Physical Chemistry B
Volume114
Issue number8
DOIs
StatePublished - Mar 4 2010

Fingerprint

Dynamic analysis
Peptides
Melting point
Conformations
Molecular dynamics
molecular dynamics
Coulomb interactions
Discrete Fourier transforms
Hydrogen bonds
Stabilization
interactions
Proteins
Computer simulation
Polytetrafluoroethylene
Dimethyl Sulfoxide
peptides
melting
methylidyne
Temperature
YYDPETGTWY

All Science Journal Classification (ASJC) codes

  • Physical and Theoretical Chemistry
  • Materials Chemistry
  • Surfaces, Coatings and Films

Cite this

Molecular dynamics analysis of the conformations of a β-hairpin miniprotein. / Hatfield, Marcus P D; Murphy, Richard F.; Lovas, Sándor.

In: Journal of Physical Chemistry B, Vol. 114, No. 8, 04.03.2010, p. 3028-3037.

Research output: Contribution to journalArticle

Hatfield, Marcus P D ; Murphy, Richard F. ; Lovas, Sándor. / Molecular dynamics analysis of the conformations of a β-hairpin miniprotein. In: Journal of Physical Chemistry B. 2010 ; Vol. 114, No. 8. pp. 3028-3037.
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