Structure, energetics and dynamics in crowded amino acid solutions: a molecular dynamics study

Area of Science:

• Computational chemistry
• Biophysics
• Solution theory

Background:

• Understanding molecular crowding is crucial for biomolecular processes.
• Accurate molecular modeling requires precise representation of crowded environments.
• Previous force fields showed limitations in modeling intermolecular interactions and aggregation.

Purpose of the Study:

• To assess the performance of a reparameterized force field in concentrated crowded solutions.
• To investigate hydration shell structure, energetics, and dynamics in crowded environments.
• To improve the accuracy of predicting bulk thermodynamic and kinetic properties.

Main Methods:

• Molecular dynamics simulations of crowded aqueous solutions.
• Utilized a modified AMBER ff99SB-ILDN force field.
• Studied five zwitterionic neutral amino acids (Gly, Ala, Thr, Pro, Ser).

Main Results:

• Improved reproducibility of osmotic coefficients, density, viscosity, and self-diffusivity.
• Enhanced solute solvation shell structuring and interaction energy.
• Reduced artificial aggregation, evidenced by radial distribution functions.
• Observed weakened water hydrogen bonding and anomalous water diffusion at short timescales.

Conclusions:

• The modified force field accurately predicts bulk solution properties in crowded environments.
• Accurate modeling of crowded solutions is essential for understanding biomolecular behavior.
• Findings highlight anomalous hydration behavior of water in crowded solutions.
• Provides a robust approach for modeling crowded molecular solutions.