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. 2005 May 10;102(19):6765-70.
doi: 10.1073/pnas.0408527102. Epub 2005 Mar 30.

Simulations of the pressure and temperature unfolding of an alpha-helical peptide

Dietmar Paschek  1 , S Gnanakaran, Angel E Garcia
Affiliations

Simulations of the pressure and temperature unfolding of an alpha-helical peptide

Dietmar Paschek et al. Proc Natl Acad Sci U S A. .

Abstract

We study by molecular simulations the reversible folding/unfolding equilibrium as a function of density and temperature of a solvated alpha-helical peptide. We use an extension of the replica exchange molecular dynamics method that allows for density and temperature Monte Carlo exchange moves. We studied 360 thermodynamic states, covering a density range from 0.96 to 1.14 g.cm(-3) and a temperature range from 300 to 547.6 K. We simulated 10 ns per replica for a total simulation time of 3.6 micros. We characterize the structural, thermodynamic, and hydration changes as a function of temperature and pressure. We also calculate the compressibility and expansivity of unfolding. We find that pressure does not affect the helix-coil equilibrium significantly and that the volume change upon pressure unfolding is small and negative (-2.3 ml/mol). However, we find significant changes in the coordination of water molecules to the backbone carbonyls. This finding predicts that changes in the chemical shifts and IR spectra with pressure can be due to changes in coordination and not only changes in the helical content. A simulation of the IR spectrum shows that water coordination effects on frequency shifts are larger than changes due to elastic structural changes in the peptide.

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Figures

Fig. 1.
Fig. 1.
Helical content of AK peptide as a function of temperature and density. The color contours with dashed lines show the helical content increments of 2.5%. The color gradient from red to blue represents high to low helical content. The average pressure at the corresponding temperature and density is marked on the contour plot with solid lines.
Fig. 2.
Fig. 2.
Radius of gyration as a function of pressure is shown at four representative temperatures (300, 323, 406, and 537 K). The error bar shows SEM obtained from 1-ns block analysis.
Fig. 3.
Fig. 3.
Pressure-dependence of the average coordination number of water to the backbone carbonyl oxygen. Insets show the average water coordination number as a function of density and temperature to the carbonyls of two specific residues: residues 11 and 12, which are positions where the carbonyl is shielded and unshielded from water, respectively, by the lysine side chain. The color schemes are the same in both contours where increase in coordination corresponds to color gradient from blue to red.
Fig. 4.
Fig. 4.
Temperature and pressure dependence of the amide-I band of the AK peptide. (a) The simulated amide-I band at four values of pressure and temperature (low T, low-P; low T, high P; high T, low P; and high T, high P). The dark and gray lines show pressure dependence at low (300 K) and high (547 K) temperatures. The solid and dashed lines correspond to low (ρ = 1.0 g·cm–3) and high (ρ = 1.14 g·cm–3) densities. (b and c) Plots correspond to the contribution from the internal (helical) (b) and external (solvent) (c) hydrogen bonding to the amide-I frequency. These contributions will lower the amide-I frequency of the individual carbonyls by the frequency shift given in cm–1.
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