Peptide aggregation and solvent electrostriction in a simple zwitterionic dipeptide via molecular dynamics...

Area of Science:

• Computational chemistry
• Biophysics
• Solution chemistry

Background:

• Understanding dipeptide behavior in aqueous solution is crucial for molecular dynamics simulations.
• Previous studies have utilized neutron diffraction to investigate peptide-water interactions.

Purpose of the Study:

• To investigate the structure of glycyl-l-alanine dipeptide in aqueous solution using molecular dynamics simulations.
• To compare simulation results with experimental neutron diffraction data.
• To assess the influence of different water models on the predicted solution structure.

Main Methods:

• Atomistic molecular dynamics simulations using the CHARMM22 force field.
• Comparison of simulation data with experimental neutron diffraction data via the static structure factor S(Q).
• Investigation of water models (TIP3P, TIP4P, SPC/E) and their impact on solution structure.

Main Results:

• Good agreement between simulations and experiments for the static structure factor S(Q), with some model-dependent variations.
• Peptide aggregation is primarily driven by hydrophilic hydrogen bonds, though simulations suggest lower aggregation degrees than experiments.
• Hydrophobic association is not significant; hydrophobic hydration is preferred.
• Bifurcated solute structural motifs may be artifacts of the CHARMM force field.
• An electrostrictive effect in water structure was observed, with implications for high-pressure compression behavior.

Conclusions:

• Classical force fields like CHARMM22 may provide flawed descriptions of molecular fluids due to potential artifacts in solute structural motifs.
• The CHARMM force field appears to overhydrate the terminal carboxy group, leading to bifurcated hydrogen bonds.
• The study provides insights into water structure and the electrostrictive effect, linking it to high-pressure compression phenomena.