How protein hydration depends on amino acid composition, peptide conformation, and force fields

Area of Science:

• Biophysics
• Structural Biology
• Computational Biology

Background:

• The protein hydration shell is crucial for biological processes like molecular recognition and protein folding.
• Understanding how surface amino acids dictate hydration shell structure is essential but not well-established.

Purpose of the Study:

• To quantify the specific contributions of all 20 proteinogenic amino acids to the hydration shell structure of globular and intrinsically disordered proteins.
• To investigate the hydration shell's effect on protein radius of gyration and electron density contrast using small-angle X-ray scattering (SAXS) predictions.

Main Methods:

• Utilized molecular dynamics simulations combined with explicit-solvent SAXS curve predictions.
• Analyzed the globular GB3 domain and the intrinsically disordered protein (IDP) XAO.
• Derived an amino acid-specific contrast score to assess hydration shell properties.

Main Results:

• Acidic, cationic, and polar residues increase water density, while apolar residues create water-depleted layers.
• Hydration shells are weaker around the IDP XAO compared to the globular GB3 domain, suggesting unfavorable water-peptide interactions.
• The impact of hydration on the IDP's radius of gyration is highly dependent on its conformation.

Conclusions:

• Protein hydration shell structure is determined by the type and arrangement of solvent-exposed amino acids.
• These findings have implications for understanding protein function, biological processes, and interpreting solution scattering data.