Electrostatic complementarity between proteins and ligands. 1. Charge disposition, dielectric and interface effects

Area of Science:

• Biochemistry
• Structural Biology
• Computational Chemistry

Background:

• Electrostatic interactions are crucial for ligand-receptor binding.
• Previous understanding of electrostatic complementarity is largely qualitative.
• Rigorous quantitative analysis is needed.

Purpose of the Study:

• To quantitatively assess electrostatic complementarity between ligands and receptors.
• To investigate the role of adjacent atoms and surface regions in complementarity.
• To evaluate the impact of dielectric models on complementarity calculations.

Main Methods:

• Utilized 34 high-quality datasets from the Brookhaven Protein Data Bank.
• Calculated electrostatic complementarity based on surface potentials.
• Compared complementarity across total ligand surface, interfacial regions, and adjacent atoms.
• Assessed the effect of homogeneous versus distance-dependent dielectric models.

Main Results:

• Electrostatic complementarity is absent between adjacent or neighboring ligand and receptor atoms.
• Little difference observed between complementarity on the total ligand surface and the interfacial region.
• Distance-dependent dielectrics slightly reduce complementarity but do not alter its overall pattern.

Conclusions:

• The study provides a rigorous, quantitative assessment of electrostatic complementarity.
• Findings challenge the notion of significant electrostatic complementarity at the atomic level between interacting partners.
• The choice of dielectric model has a minor impact on the observed complementarity patterns.