Polarizable molecular dynamics simulations of aqueous dipeptides

Area of Science:

• Computational chemistry
• Biomolecular simulations
• Physical chemistry

Background:

• Dipeptides form concentrated aqueous solutions.
• Understanding peptide aggregation is crucial for biomolecular studies.
• Force fields are used to model molecular interactions.

Purpose of the Study:

• To assess the effects of polarizable force fields on molecular dynamics simulations of dipeptide solutions.
• To compare simulation results with experimental data, including neutron diffraction.
• To determine the adequacy of polarizable and nonpolarizable models in reproducing peptide aggregation.

Main Methods:

• Molecular dynamics (MD) simulations of concentrated aqueous solutions of Gly-Ala, Gly-Pro, and Ala-Pro dipeptides.
• Utilized both polarizable and nonpolarizable force fields for comparison.
• Analyzed solute and solvent structure and dynamics.
• Compared simulation outputs with experimental neutron diffraction data.

Main Results:

• Polarizable water molecules showed depolarization in concentrated peptide solutions, adapting to electrostatic environments.
• Significant differences in water structure and dynamics were observed between polarizable and nonpolarizable models.
• The polarizable model exhibited more realistic water structure and dynamics, indicating enhanced peptide-water interactions.
• Neither force field model accurately reproduced the experimentally observed dipeptide aggregation behavior.

Conclusions:

• Polarizable force fields offer a more accurate representation of water's behavior in concentrated peptide solutions.
• Current polarizable and nonpolarizable models are insufficient for accurately predicting dipeptide aggregation.
• Further development of computational models is required for precise biomolecular simulations.