A rush to explore protein-ligand electrostatic interaction energy with Charger

Area of Science:

• Computational chemistry
• Molecular modeling
• Structural biology

Background:

• Calculating accurate electrostatic interaction energy is challenging due to electron density overlap.
• Traditional numerical methods (nEP/MM) are computationally expensive, especially at short distances.

Purpose of the Study:

• Introduce the Charger software library implementing the analytical exact potential and multipole moment (aEP/MM) method.
• Evaluate the efficiency and accuracy of Charger for molecular electrostatic calculations.
• Apply Charger to analyze protein-ligand electrostatic interactions and guide mutation design.

Main Methods:

• Implementation of the analytical exact potential and multipole moment (aEP/MM) method in the Charger library.
• Benchmark testing on small molecules (C, H, N, O) and protein-ligand complexes (including sulfur atoms).
• Application to Glutathione transferase (GST) complexed with a benzophenone ligand.

Main Results:

• Charger achieves up to two orders of magnitude speed improvement over nEP/MM with high accuracy.
• The software accurately calculates protein-ligand interaction energies, even with sulfur atoms.
• Analysis of GST-benzophenone complex identified residues stabilizing and hindering ligand binding.

Conclusions:

• Charger provides an efficient and accurate tool for electrostatic interaction energy calculations.
• The method facilitates detailed analysis of protein-ligand electrostatic interactions.
• Charger can guide rational design of mutations to optimize protein-ligand binding by addressing electrostatic factors.