Multipole models of sulphur for accurate anisotropic electrostatic interactions within force fields

Area of Science:

• Computational chemistry
• Molecular modeling
• Drug discovery

Background:

• Advancements in computing power drive innovation in computational chemistry for drug discovery.
• Distributed multipole expansion successfully models electrostatic interactions in halogen bonding (XB).
• Extending electrostatic modeling to sulphur-based chalcogen bonding presents a significant challenge.

Purpose of the Study:

• To develop and test anisotropic models for sulphur-based chalcogen bonding.
• To improve the accuracy of molecular mechanics force fields in predicting molecular interactions.
• To enhance computational drug discovery predictions.

Main Methods:

• Derived and tested 11 anisotropic models for sulphur-based interactions.
• Evaluated model performance against ab initio molecular electrostatic potential.
• Selected three promising models for integration into the General Amber Force Field (GAFF).

Main Results:

• Anisotropic models demonstrated improved accuracy in reproducing molecular electrostatic potential compared to isotropic models.
• The developed models successfully differentiated σ-hole interactions from other molecular directions.
• Selected models showed potential for refining electrostatic force fields.

Conclusions:

• Anisotropic models offer a promising approach to accurately describe sulphur-based chalcogen bonding.
• These models can correct inaccuracies in existing force fields that rely solely on isotropic charges.
• Further development of refined electrostatic force fields is warranted for enhanced drug discovery applications.