Joint neighbors approximation of macromolecular solvent accessible surface area

Area of Science:

• Computational chemistry
• Biophysics
• Molecular modeling

Background:

• Accurate calculation of solvent accessible surface area (SASA) is crucial for understanding molecular interactions and properties.
• Existing approximate methods often rely on empirical parameters, limiting their generalizability.
• The need for a versatile and accurate SASA calculation method applicable to diverse molecular structures and states persists.

Purpose of the Study:

• To develop a novel, parameter-free approximate analytical method for calculating SASA and its gradients.
• To ensure the method's applicability to arbitrary molecules in various conformations (folded and unfolded).
• To achieve computational efficiency comparable to existing exact analytical methods.

Main Methods:

• A recursive procedure for pairwise joining of neighboring atoms was employed.
• The method calculates approximate analytical SASA and its gradients with respect to atomic coordinates.
• No empirical parameters are used in the calculation process.

Main Results:

• The developed method demonstrates comparable accuracy to exact analytical methods for SASA calculations.
• Average errors in absolute atomic surface area are approximately 1 Ų for folded protein conformations.
• For unfolded protein conformations, average errors range from 1.65 to 1.87 Ų.
• Computational times are similar to the fast exact analytical method GETAREA.

Conclusions:

• The new approximate analytical method provides accurate SASA calculations without empirical parameters.
• Its versatility allows for reliable application to macromolecules in both folded and unfolded states.
• The method offers a computationally efficient alternative for SASA determination in molecular modeling.