Quantifying water hydrogen bonding from the surface electrostatic potential at varying iso-density contours

Area of Science:

• Computational chemistry
• Molecular modeling
• Structural biology

Background:

• Water's unique electrostatic properties enable versatile hydrogen bonding.
• Understanding water interactions is crucial in various chemical and biological systems.
• Previous methods for analyzing water interactions were often complex and computationally intensive.

Purpose of the Study:

• To investigate and visualize water interactions using electrostatic potential (ESP) mapped onto electron density contours.
• To demonstrate the utility of ESP in evaluating favorable and unfavorable interactions.
• To establish a generalized model for water interactions applicable across different systems.

Main Methods:

• Calculation and visualization of electrostatic potential on varying electron density contours.
• Analysis of water interactions in small molecule models, lactose crystals, and protein-protein interfaces.
• Evaluation of interaction strength and visualization of favorable/unfavorable interactions.

Main Results:

• Water exhibits a balanced electrostatic potential, allowing equal capacity for hydrogen bond donation and acceptance.
• ESP mapping effectively visualizes water-mediated interactions, revealing their general form across diverse systems.
• A strong correlation exists between ESP and interaction strength, suggesting its use in scoring functions.

Conclusions:

• Water acts as a neutral agent in interactions, with its role determined by the partner molecule.
• ESP mapping provides a unified and efficient approach for analyzing water interactions.
• This method holds promise for improving molecular modeling and structure validation accuracy.