Abstract
The stability of secondary structure motifs found in proteins is influenced by the choice of the configuration of the chiral centers present in the amino acid residues (i.e., D vs L). Experimental studies showed that the structural properties of the tetrapeptide LV LP LA LL (all-L) are drastically altered upon mutating the L-proline and the L-alanine by their D-enantiomers [J. Am. Chem. Soc. 1996, 118, 6975]. The all-L diastereomer is unstructured, experiencing little or no β-hairpin formation, while the LV DP DA LL peptide exhibits a substantial population of β-hairpin conformation. In this study, we perform molecular dynamics simulations to investigate the folding propensity of these two model peptides. The results confirm the experimental findings, namely, that the presence of D-amino acids in the loop region strongly induces β-hairpin formation (a population increase from about 1.5% to 50% is observed). The major factor determining the different behavior is found to be the large difference in energy between the two diastereomers, approximately 22 kJ/mol, when they adopt a β-hairpin structure. The higher energy observed for the all-L peptide is a consequece of none-ideal hydrogen bond formation and of steric repulsions. The results suggest that selective incorporation of D-amino acids in proteins can be used to enhance certain secondary structure elements. The kinetic behavior of the folding process observed in the simulations is also investigated. We find that the decay rate of the folded structure fits to a biexponential function, suggesting that the folding/unfolding process of a β-hairpin is governed by two different mechansims.
| Original language | English |
|---|---|
| Pages (from-to) | 1281-1288 |
| Number of pages | 8 |
| Journal | Journal of Physical Chemistry B |
| Volume | 109 |
| Issue number | 3 |
| DOIs | |
| State | Published - Jan 27 2005 |
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All Science Journal Classification (ASJC) codes
- Physical and Theoretical Chemistry
Cite this
Characterization of the stereochemical selectivity of β-hairpin formation by molecular dynamics simulations. / Soto, Patricia; Zangi, Ronen.
In: Journal of Physical Chemistry B, Vol. 109, No. 3, 27.01.2005, p. 1281-1288.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Characterization of the stereochemical selectivity of β-hairpin formation by molecular dynamics simulations
AU - Soto, Patricia
AU - Zangi, Ronen
PY - 2005/1/27
Y1 - 2005/1/27
N2 - The stability of secondary structure motifs found in proteins is influenced by the choice of the configuration of the chiral centers present in the amino acid residues (i.e., D vs L). Experimental studies showed that the structural properties of the tetrapeptide LV LP LA LL (all-L) are drastically altered upon mutating the L-proline and the L-alanine by their D-enantiomers [J. Am. Chem. Soc. 1996, 118, 6975]. The all-L diastereomer is unstructured, experiencing little or no β-hairpin formation, while the LV DP DA LL peptide exhibits a substantial population of β-hairpin conformation. In this study, we perform molecular dynamics simulations to investigate the folding propensity of these two model peptides. The results confirm the experimental findings, namely, that the presence of D-amino acids in the loop region strongly induces β-hairpin formation (a population increase from about 1.5% to 50% is observed). The major factor determining the different behavior is found to be the large difference in energy between the two diastereomers, approximately 22 kJ/mol, when they adopt a β-hairpin structure. The higher energy observed for the all-L peptide is a consequece of none-ideal hydrogen bond formation and of steric repulsions. The results suggest that selective incorporation of D-amino acids in proteins can be used to enhance certain secondary structure elements. The kinetic behavior of the folding process observed in the simulations is also investigated. We find that the decay rate of the folded structure fits to a biexponential function, suggesting that the folding/unfolding process of a β-hairpin is governed by two different mechansims.
AB - The stability of secondary structure motifs found in proteins is influenced by the choice of the configuration of the chiral centers present in the amino acid residues (i.e., D vs L). Experimental studies showed that the structural properties of the tetrapeptide LV LP LA LL (all-L) are drastically altered upon mutating the L-proline and the L-alanine by their D-enantiomers [J. Am. Chem. Soc. 1996, 118, 6975]. The all-L diastereomer is unstructured, experiencing little or no β-hairpin formation, while the LV DP DA LL peptide exhibits a substantial population of β-hairpin conformation. In this study, we perform molecular dynamics simulations to investigate the folding propensity of these two model peptides. The results confirm the experimental findings, namely, that the presence of D-amino acids in the loop region strongly induces β-hairpin formation (a population increase from about 1.5% to 50% is observed). The major factor determining the different behavior is found to be the large difference in energy between the two diastereomers, approximately 22 kJ/mol, when they adopt a β-hairpin structure. The higher energy observed for the all-L peptide is a consequece of none-ideal hydrogen bond formation and of steric repulsions. The results suggest that selective incorporation of D-amino acids in proteins can be used to enhance certain secondary structure elements. The kinetic behavior of the folding process observed in the simulations is also investigated. We find that the decay rate of the folded structure fits to a biexponential function, suggesting that the folding/unfolding process of a β-hairpin is governed by two different mechansims.
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U2 - 10.1021/jp045729z
DO - 10.1021/jp045729z
M3 - Article
VL - 109
SP - 1281
EP - 1288
JO - Journal of Physical Chemistry B Materials
JF - Journal of Physical Chemistry B Materials
SN - 1520-6106
IS - 3
ER -