Fully atomistic multiscale polarizable quantum mechanics (QM)/molecular mechanics (MM) approaches, combined with techniques to sample the solute-solvent phase space, constitute the most accurate method to compute spectral signals in aqueous solution. Conventional sampling strategies, such as classical molecular dynamics (MD), may encounter drawbacks when the conformational space is particularly complex, and transition barriers between conformers are high. This can lead to inaccurate sampling, which can potentially impact the accuracy of spectral calculations. For this reason, in this work, we compare classical MD with enhanced sampling techniques, i.e., replica exchange MD and metadynamics. In particular, we show how the different sampling techniques affect computed UV, electronic circular dichroism, nuclear magnetic resonance shielding, and optical rotatory dispersion of N-acetylproline-amide in aqueous solution. Such a system is a model peptide characterized by complex conformational variability. Calculated values suggest that spectral properties are influenced by solute conformers, relative population, and solvent effects; therefore, particular care needs to be paid for when choosing the sampling technique.

Computational Spectroscopy of Aqueous Solutions : The Underlying Role of Conformational Sampling

Sepali, Chiara;Gomez Maya, Sara;Grifoni, Emanuele;Giovannini, Tommaso;Cappelli, Chiara
2024

Abstract

Fully atomistic multiscale polarizable quantum mechanics (QM)/molecular mechanics (MM) approaches, combined with techniques to sample the solute-solvent phase space, constitute the most accurate method to compute spectral signals in aqueous solution. Conventional sampling strategies, such as classical molecular dynamics (MD), may encounter drawbacks when the conformational space is particularly complex, and transition barriers between conformers are high. This can lead to inaccurate sampling, which can potentially impact the accuracy of spectral calculations. For this reason, in this work, we compare classical MD with enhanced sampling techniques, i.e., replica exchange MD and metadynamics. In particular, we show how the different sampling techniques affect computed UV, electronic circular dichroism, nuclear magnetic resonance shielding, and optical rotatory dispersion of N-acetylproline-amide in aqueous solution. Such a system is a model peptide characterized by complex conformational variability. Calculated values suggest that spectral properties are influenced by solute conformers, relative population, and solvent effects; therefore, particular care needs to be paid for when choosing the sampling technique.
2024
Settore CHIM/02 - Chimica Fisica
Circular dichroism spectroscopy; Computer simulations; Molecular structure,Solution chemistry; Solvents
   Tuscany Health Ecosystem
   European Union
   Next Generation EU
   ECS00000017
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11384/142203
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