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 language | English |
|---|---|
| Pages (from-to) | 3028-3037 |
| Number of pages | 10 |
| Journal | Journal of Physical Chemistry B |
| Volume | 114 |
| Issue number | 8 |
| DOIs | |
| State | Published - Mar 4 2010 |
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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 journal › Article
}
TY - JOUR
T1 - Molecular dynamics analysis of the conformations of a β-hairpin miniprotein
AU - Hatfield, Marcus P D
AU - Murphy, Richard F.
AU - Lovas, Sándor
PY - 2010/3/4
Y1 - 2010/3/4
N2 - 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.
AB - 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.
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U2 - 10.1021/jp910465e
DO - 10.1021/jp910465e
M3 - Article
VL - 114
SP - 3028
EP - 3037
JO - Journal of Physical Chemistry B Materials
JF - Journal of Physical Chemistry B Materials
SN - 1520-6106
IS - 8
ER -