TY - JOUR
T1 - The Conformation and Aggregation of Proline-Rich Surfactant-Like Peptides
AU - Hamley, Ian W.
AU - Castelletto, Valeria
AU - Dehsorkhi, Ashkan
AU - Torras, Juan
AU - Aleman, Carlos
AU - Portnaya, Irina
AU - Danino, Dganit
N1 - Publisher Copyright:
© 2018 American Chemical Society.
PY - 2018/2/15
Y1 - 2018/2/15
N2 - The secondary structure of proline-rich surfactant-like peptides is examined for the first time and is found to be influenced by charged end groups in peptides P6K, P6E, and KP6E and an equimolar mixture of P6K and P6E. The peptides exhibit a conformational transition from unordered to polyproline II (PPII) above a critical concentration, detected from circular dichroism (CD) measurements and unexpectedly from fluorescence dye probe measurements. Isothermal titration calorimetry (ITC) measurements provided the Gibbs energies of hydration of P6K and P6E, which correspond essentially to the hydration energies of the terminal charged residues. A detailed analysis of peptide conformation for these peptides was performed using density functional theory calculations, and this was used as a basis for hybrid quantum mechanics/molecular mechanics molecular dynamics (QM/MM MD) simulations. Quantum mechanics simulations in implicit water show both peptides (and their 1:1 mixture) exhibit PPII conformations. However, hybrid QM/MM MD simulations suggest that some deviations from this conformation are present for P6K and P6E in peptide bonds close to the charged residue, whereas in the 1:1 mixture a PPII structure is observed. Finally, aggregation of the peptides was investigated using replica exchange molecular dynamics simulations. These reveal a tendency for the average aggregate size (as measured by the radius of gyration) to increase with increasing temperature, which is especially marked for P6K, although the fraction of the most populated clusters is larger for P6E.
AB - The secondary structure of proline-rich surfactant-like peptides is examined for the first time and is found to be influenced by charged end groups in peptides P6K, P6E, and KP6E and an equimolar mixture of P6K and P6E. The peptides exhibit a conformational transition from unordered to polyproline II (PPII) above a critical concentration, detected from circular dichroism (CD) measurements and unexpectedly from fluorescence dye probe measurements. Isothermal titration calorimetry (ITC) measurements provided the Gibbs energies of hydration of P6K and P6E, which correspond essentially to the hydration energies of the terminal charged residues. A detailed analysis of peptide conformation for these peptides was performed using density functional theory calculations, and this was used as a basis for hybrid quantum mechanics/molecular mechanics molecular dynamics (QM/MM MD) simulations. Quantum mechanics simulations in implicit water show both peptides (and their 1:1 mixture) exhibit PPII conformations. However, hybrid QM/MM MD simulations suggest that some deviations from this conformation are present for P6K and P6E in peptide bonds close to the charged residue, whereas in the 1:1 mixture a PPII structure is observed. Finally, aggregation of the peptides was investigated using replica exchange molecular dynamics simulations. These reveal a tendency for the average aggregate size (as measured by the radius of gyration) to increase with increasing temperature, which is especially marked for P6K, although the fraction of the most populated clusters is larger for P6E.
UR - http://www.scopus.com/inward/record.url?scp=85042158983&partnerID=8YFLogxK
U2 - 10.1021/acs.jpcb.7b11463
DO - 10.1021/acs.jpcb.7b11463
M3 - 文章
C2 - 29357666
AN - SCOPUS:85042158983
SN - 1520-6106
VL - 122
SP - 1826
EP - 1835
JO - Journal of Physical Chemistry B
JF - Journal of Physical Chemistry B
IS - 6
ER -