An improved methodology to compute surface site interaction points using high density molecular electrostatic...

Area of Science:

• Computational Chemistry
• Materials Science

Background:

• Surface Site Interaction Points (SSIP) are crucial for understanding molecular interactions in condensed phases.
• Previous SSIP calculations have shown success but require optimization for efficiency and precision.

Purpose of the Study:

• To develop optimized methods for calculating SSIP using Molecular Electrostatic Potential Surfaces (MEPS).
• To enhance the accuracy and speed of SSIP determination for improved computational chemistry applications.

Main Methods:

• Utilized Density Functional Theory (DFT) with B3LYP/6-31*G basis set to compute MEPS.
• Implemented optimizations based on correlating experimental H-bond parameters (α and β) with MEPS extremes across various electron density levels.
• Performed parameterization as a function of atom types.

Main Results:

• MEPS calculated at 0.01 au electron density level showed slightly improved correlation with experimental data compared to other density values.
• The optimized method demonstrated significant improvements in the correlation between theoretical and experimental data.
• The 0.01 au calculation is approximately six times faster than calculations at 0.002 au.

Conclusions:

• The proposed methodology provides a fast and precise way to obtain SSIP.
• Enhanced SSIP calculations can significantly improve applications such as virtual cocrystal screening, free energy calculations in solution, and molecular docking.