Quantitative electrostatic force tomography for virus capsids in interaction with an approaching nanoscale probe

Area of Science:

• Biophysics
• Structural Biology
• Computational Biology

Background:

• Electrostatic interactions are vital for viral capsid assembly, disassembly, and stability.
• Understanding capsid protein organization under nanoprobe interaction is a key challenge in biomacromolecular research.

Purpose of the Study:

• To develop and validate a generalized electrostatic model for quantifying subnanometric interactions between AFM tips and proteinaceous viral capsids.
• To identify specific amino acids and atoms contributing to interaction forces and analyze capsid-tip interactions using tomography.

Main Methods:

• A generalized electrostatic model based on the Poisson-Boltzmann equation was developed.
• The model quantifies subnanometric electrostatic interactions from molecular snapshots.
• Validation was performed against previous semi-empirical models for electrostatic forces.

Main Results:

• The model successfully quantifies electrostatic interactions and identifies contributions of specific amino acids and atoms.
• Validation confirmed accuracy of total electrostatic forces at length scales greater than 1 nm.
• Analysis of Zika capsid interactions revealed localized interaction sites and identified key residues and atoms.

Conclusions:

• The developed electrostatic model provides a method for interpreting force microscopy experiments on viral capsids.
• This approach has applications in virological characterization and nanomedicine, including targeted drug delivery and nucleic acid delivery systems.