An extended aqueous solvation model based on atom-weighted solvent accessible surface areas: SAWSA v2.0 model

Area of Science:

• Computational Chemistry
• Physical Chemistry
• Molecular Modeling

Background:

• Calculating aqueous solvation free energy is crucial for understanding molecular interactions and predicting chemical behavior.
• Existing models often struggle with accuracy, especially for macromolecules like proteins.

Purpose of the Study:

• To develop a novel, accurate, and broadly applicable method for calculating aqueous solvation free energy.
• To improve upon existing solvation models, particularly for small organic molecules and proteins.

Main Methods:

• Developed the SAWSA v2.0 (atom-weighted solvent accessible surface area) method.
• Utilized multivariate regression analysis with experimental solvation free energy data.
• Applied distinct atom typing rules and fitting processes for small organic molecules and proteins.
• Compared SAWSA v2.0 against six other established solvation models.

Main Results:

• SAWSA v2.0 achieved a correlation coefficient of 0.984 and an absolute mean error of 0.40 kcal/mol for neutral organic molecules.
• The model demonstrated superior performance compared to previous SAWSA and other models for organic molecules.
• For proteins, SAWSA v2.0 showed good agreement with PB/SA models and outperformed other protein-specific models.

Conclusions:

• SAWSA v2.0 offers a significant advancement in calculating aqueous solvation free energies for diverse chemical species.
• The method provides a more accurate and reliable alternative to existing solvation models.
• The atom-weighted approach effectively captures the complexities of solvation for both small molecules and large biomolecules.