Unveiling Vibrational Couplings in Model Peptides in Solution by a Theoretical Approach

Vibrational analysis of peptides in solution and the theoretical determination of the effects of the microenvironment on infrared and Raman spectra are of key importance in many fields of chemical interest. In this work, we present a computational study combining static quantum mechanical calculatio...

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Main Authors: Federico Coppola, Fulvio Perrella, Alessio Petrone, Greta Donati, Luciana Marinelli, Nadia Rega
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/30/13/2854
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author Federico Coppola
Fulvio Perrella
Alessio Petrone
Greta Donati
Luciana Marinelli
Nadia Rega
author_facet Federico Coppola
Fulvio Perrella
Alessio Petrone
Greta Donati
Luciana Marinelli
Nadia Rega
author_sort Federico Coppola
collection DOAJ
description Vibrational analysis of peptides in solution and the theoretical determination of the effects of the microenvironment on infrared and Raman spectra are of key importance in many fields of chemical interest. In this work, we present a computational study combining static quantum mechanical calculations with ab initio molecular dynamics simulations to investigate the vibrational behavior of three peptide models in both the gas phase and in explicit water, under non-periodic boundary conditions. The vibrational spectra of the main amide bands, namely amide I-III and A, were analyzed using a time–frequency approach based on the wavelet transform, which allows the resolution of transient frequency shifts and mode couplings along the trajectories. This combined approach enabled us to perform a time-resolved vibrational analysis revealing how vibrational frequencies, especially of the C=O and N–H stretching modes, evolve over time due to dynamical microsolvation. These fluctuations modulate vibrational couplings and lead to spectral broadening and frequency shifts that correlate with the local structuring of the solvent. In conclusion, our results highlight how the proposed protocol allows for the direct connection between vibrational modes and local structural changes, providing a link from the spectroscopic observable to the structure, the peptide backbone, and its microenvironment.
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spelling doaj-art-73ece93deb234c0da575bce43e18ff692025-08-20T03:50:16ZengMDPI AGMolecules1420-30492025-07-013013285410.3390/molecules30132854Unveiling Vibrational Couplings in Model Peptides in Solution by a Theoretical ApproachFederico Coppola0Fulvio Perrella1Alessio Petrone2Greta Donati3Luciana Marinelli4Nadia Rega5Scuola Superiore Meridionale, Largo San Marcellino 10, I-80138 Napoli, ItalyScuola Superiore Meridionale, Largo San Marcellino 10, I-80138 Napoli, ItalyScuola Superiore Meridionale, Largo San Marcellino 10, I-80138 Napoli, ItalyDepartment of Pharmacy, University of Napoli Federico II, Via Domenico Montesano 49, I-80131 Napoli, ItalyDepartment of Pharmacy, University of Napoli Federico II, Via Domenico Montesano 49, I-80131 Napoli, ItalyScuola Superiore Meridionale, Largo San Marcellino 10, I-80138 Napoli, ItalyVibrational analysis of peptides in solution and the theoretical determination of the effects of the microenvironment on infrared and Raman spectra are of key importance in many fields of chemical interest. In this work, we present a computational study combining static quantum mechanical calculations with ab initio molecular dynamics simulations to investigate the vibrational behavior of three peptide models in both the gas phase and in explicit water, under non-periodic boundary conditions. The vibrational spectra of the main amide bands, namely amide I-III and A, were analyzed using a time–frequency approach based on the wavelet transform, which allows the resolution of transient frequency shifts and mode couplings along the trajectories. This combined approach enabled us to perform a time-resolved vibrational analysis revealing how vibrational frequencies, especially of the C=O and N–H stretching modes, evolve over time due to dynamical microsolvation. These fluctuations modulate vibrational couplings and lead to spectral broadening and frequency shifts that correlate with the local structuring of the solvent. In conclusion, our results highlight how the proposed protocol allows for the direct connection between vibrational modes and local structural changes, providing a link from the spectroscopic observable to the structure, the peptide backbone, and its microenvironment.https://www.mdpi.com/1420-3049/30/13/2854ab initio molecular dynamicsDFTmodel peptideshydrogen bonding in aqueous solutionsolvent effects on vibrational dynamicsenvironmental effects
spellingShingle Federico Coppola
Fulvio Perrella
Alessio Petrone
Greta Donati
Luciana Marinelli
Nadia Rega
Unveiling Vibrational Couplings in Model Peptides in Solution by a Theoretical Approach
Molecules
ab initio molecular dynamics
DFT
model peptides
hydrogen bonding in aqueous solution
solvent effects on vibrational dynamics
environmental effects
title Unveiling Vibrational Couplings in Model Peptides in Solution by a Theoretical Approach
title_full Unveiling Vibrational Couplings in Model Peptides in Solution by a Theoretical Approach
title_fullStr Unveiling Vibrational Couplings in Model Peptides in Solution by a Theoretical Approach
title_full_unstemmed Unveiling Vibrational Couplings in Model Peptides in Solution by a Theoretical Approach
title_short Unveiling Vibrational Couplings in Model Peptides in Solution by a Theoretical Approach
title_sort unveiling vibrational couplings in model peptides in solution by a theoretical approach
topic ab initio molecular dynamics
DFT
model peptides
hydrogen bonding in aqueous solution
solvent effects on vibrational dynamics
environmental effects
url https://www.mdpi.com/1420-3049/30/13/2854
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AT alessiopetrone unveilingvibrationalcouplingsinmodelpeptidesinsolutionbyatheoreticalapproach
AT gretadonati unveilingvibrationalcouplingsinmodelpeptidesinsolutionbyatheoreticalapproach
AT lucianamarinelli unveilingvibrationalcouplingsinmodelpeptidesinsolutionbyatheoreticalapproach
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