On the inverse temperature transition and development of an entropic elastomeric force of the elastin mimetic peptide [LGGVG](3, 7)

Abstract

We report on a molecular dynamics simulation based study of the thermal and mechanical properties of the elastin mimetic peptide [LGGVG](n) (n = 3, 7). Our findings indicate that this peptide undergoes an inverse temperature transition as the temperature is raised from ~20 °C to 42 °C. The thermal behavior is similar to what has been observed in other well studied short mimetic peptides of elastin. Both [LGGVG](n) (n = 3, 7) peptides exhibit an increase in the number of side chain contacts and peptide-peptide hydrogen bonds when the temperature is raised from ~20 °C to 42 °C. These observations are accompanied by a decrease in the number of proximal water molecules and number of peptide-water hydrogen bonds. This work also reports on a comparison of the thermal and mechanical properties of [LGGVG](3) and [VPGVG](3) and quantifies the interaction with surrounding waters of hydration under mechanically strained conditions. It is demonstrated, via a quasi-harmonic approach, that both model peptides exhibit a reduction in the population of low-frequency modes and an increase in population of high-frequency modes upon elongation. The shift in population of frequency modes causes the peptide entropy to decrease upon elongation and is responsible for the development of an entropic force that gives rise to elasticity. These observations are in disagreement with a previously published notion that model elastin peptides, such as [VPGVG](18), increase in entropy upon elongation.

Figure 1

Radius of gyration of C_α for [LGGVG]₃ under (a) 50 000 kJ/mol nm² force constant at a pulling rate of 0.005 nm/ps and (b) a constant force of 20 000 kJ/mol nm.

Figure 2

RMSD averaged over all C_α for the temperatures of 10 °C, 20 °C, 35 °C, and 42^○C of (a) [VPGVG]₃ and (b) [VPGVG]₇.

Figure 3

RMSD averaged over all C_α for the temperatures of 10 °C, 20^○C, 35 °C, and 42^○C of (a) [LGGVG]₃ and (b) [LGGVG]₇.

Figure 4

Valine Ramachandran maps computed in the time range of 3–4 ns for (a) [VPGVG]₃ at 10 °C, (b) [VPGVG]₃ at 42 °C, (c) [LGGVG]₃ at 10 °C, and (d) [LGGVG]₃ at 42 °C.

Figure 5

Entropy of the [LGGVG]₃ (solid line) and [VPGVG]₃ (dashed line) peptides as a function of temperature. The entropy was estimated via the quasi-harmonic approach described in the text.

Figure 6

Entropy of the (a) [LGGVG]₃ and (b) [VPGVG]₃ peptides in relaxed and strained states as a function of the time sampling window (Δt) at 25 °C. The entropy was estimated via the quasi-harmonic approach described in the text.

Figure 7

Histograms of the harmonic oscillator frequencies of (a) [LGGVG]₃ and (b) [VPGVG]₃ in relaxed and strained states. The frequency was calculated from the eigenvalues of the mass weighted covariance matrix, by employing Eq. 2, as described in the text. The figure highlights an increase in the population at higher frequencies when the peptide is stretched, resulting in a decrease in entropy.