Spatially Resolved Single-Water Entropy around Amino Acids and Its Link to Hydropathy

Area of Science:

• Biophysics
• Computational Chemistry
• Molecular Dynamics

Background:

• The hydrophobic effect is vital for protein folding and molecular recognition.
• Enthalpy-entropy balance in hydration shells provides critical insights into biological phenomena.
• Quantifying entropic contributions at the single-particle level, especially for water molecules, is challenging.

Purpose of the Study:

• To calculate the translational and rotational entropies of water molecules surrounding amino acids.
• To compare these calculated entropies with existing theoretical studies.
• To analyze the spatial distribution and characteristics of water entropy around amino acids.

Main Methods:

• Applied a permutation reduction technique to molecular dynamics trajectories to compute single-molecule translational entropy.
• Utilized the quasiharmonic approach for translational entropy calculations.
• Calculated rotational entropy based on the angular orientation distribution of permuted water molecules.

Main Results:

• Computed translational (trans) and rotational (rot) water entropies around amino acids.
• Achieved good agreement between calculated solvation entropy and methods like thermal integration (TI) and grid inhomogeneous solvation theory (GIST).
• Observed consistent entropy loss near amino acid backbones, with charged residues causing greater reductions. Positively charged residues impacted translational entropy more, while negatively charged residues affected rotational entropy.

Conclusions:

• Developed a method to calculate individual water molecule entropies around amino acids.
• Demonstrated that total water entropy loss correlates with amino acid hydropathy index.
• Laid the foundation for calculating water entropy around proteins, enhancing understanding of hydration in biomolecular systems and molecular recognition.