Effect of the Hydration Shell on the Carbonyl Vibration in the Ala-Leu-Ala-Leu Peptide.

Irtaza Hassan,Federica Ferraro,Petra Imhof

doi:10.3390/molecules26082148

Irtaza Hassan, Federica Ferraro + Show 1 more

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https://doi.org/10.3390/molecules26082148

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Abstract

The vibrational spectrum of the Ala-Leu-Ala-Leu peptide in solution, computed from first-principles simulations, shows a prominent band in the amide I region that is assigned to stretching of carbonyl groups. Close inspection reveals combined but slightly different contributions by the three carbonyl groups of the peptide. The shift in their exact vibrational signature is in agreement with the different probabilities of these groups to form hydrogen bonds with the solvent. The central carbonyl group has a hydrogen bond probability intermediate to the other two groups due to interchanges between different hydrogen-bonded states. Analysis of the interaction energies of individual water molecules with that group shows that shifts in its frequency are directly related to the interactions with the water molecules in the first hydration shell. The interaction strength is well correlated with the hydrogen bond distance and hydrogen bond angle, though there is no perfect match, allowing geometrical criteria for hydrogen bonds to be used as long as the sampling is sufficient to consider averages. The hydrogen bond state of a carbonyl group can therefore serve as an indicator of the solvent’s effect on the vibrational frequency.

Highlights

Peptides are often used as small, tractable model systems for proteins in order to study their conformational dynamics and the dynamics of the surrounding water molecules, which play a key role in protein function [1]
We investigate the vibrational signature of the small peptide AlanineLeucine-Alanine-Leucine (ALAL) and the effect of the fluctuations of solute molecules and hydrogen bonding states on the amide I frequencies by employing a combination of first-principles Molecular dynamics (MD) simulations, fragmentation methods to quantify interaction energies, and geometrical analyses
Analysis of the MD simulations of the ALAL peptide in water with an empirical force field shows that the conformational space of the backbone torsion angles ψ, φ for definition) is well sampled and all sterically “allowed” regions in a Ramachandran plot, i.e., around the angles that define α-helix (α: φ ≈ −57◦ ; ψ ≈ −47◦ ), β-sheet (β: φ ≈ −130◦ ; ψ ≈ +140), or left-handed helix (L:φ ≈ 80◦ ; ψ ≈ +70) conformations, were visited and regions corresponding to secondary structures such as α-helix, β-sheet, or lefthanded helix, show the lowest free energies

Summary

Introduction

Peptides are often used as small, tractable model systems for proteins in order to study their conformational dynamics and the dynamics of the surrounding water molecules, which play a key role in protein function [1]. Protein or peptide dynamics take place over longer timescales, whereas the timescales of water dynamics are around picoseconds, mainly due to high mobility of water molecules and frequent changes in the hydrogen bonding state [2,3,4]. The vibrational fingerprints of this region are due to the motions of the groups involved in the peptide bond, that is, carbonyl,. While time-resolved IR spectroscopy techniques provide a time resolution that allows us to measure structural dynamics of proteins and peptides in a solvated environment on picoseconds timescales [5], the assignment of the timescales to the underlying processes, and even more the probable conformations, call for an accompanying approach

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