Solvation and cavity occupation in biomolecules.

Area of Science:

• Biophysics
• Computational Biology
• Structural Biology

Background:

• Solvation density is critical for protein dynamics and structure.
• Understanding hydration sites in proteins, especially at interfaces and in cavities, enhances knowledge of biomolecular function.
• X-ray diffraction struggles with accurate hydration structure determination, particularly for interfacial and cavity-bound water molecules.

Purpose of the Study:

• To accurately determine solvent density within the myoglobin heme cavity.
• To evaluate advanced integral equation theories and approximate methods for solvent structure analysis.
• To identify hydration sites and solvent pathways in complex protein interiors.

Main Methods:

• Utilized advances in integral equation theories for calculating angle-dependent average solvent structure.
• Employed the proximal radial distribution method for approximate solvent structure determination.
• Performed all-atom molecular dynamics simulations to determine solvent density in the myoglobin heme cavity.

Main Results:

• Identified four distinct hydration sites within the large myoglobin heme cavity.
• The identified hydration sites were not in close proximity, suggesting multiple entry/exit points.
• All three computational methods accurately reproduced the main solvation sites.

Conclusions:

• The study successfully identified key solvation sites and a solvent pathway into the myoglobin interior.
• Agreement between molecular dynamics and approximate methods indicates their computational efficiency and accuracy.
• These findings advance the understanding of protein hydration and offer validated computational approaches.