Role of Resultant Dipole Moment in Mechanical Dissociation of Biological Complexes

TL;DR

This study explores how pulling proteins along their resultant dipole moment vector in steered molecular dynamics affects their mechanical stability, revealing it as a significant factor in protein-peptide dissociation.

Contribution

The paper introduces a novel pulling direction along the resultant dipole moment vector in steered MD simulations, showing it enhances the assessment of mechanical stability of protein-peptide complexes.

Findings

Pulling along the dipole moment vector yields stronger forces.

Resultant dipole moment influences mechanical stability.

New method offers alternative to traditional unbinding directions.

Abstract

Protein-peptide interactions play essential roles in many cellular processes and their structural characterization is the major focus of current experimental and theoretical research. Two decades ago, it was proposed to employ the steered molecular dynamics to assess the strength of protein-peptide interactions. The idea behind using steered molecular dynamics simulations is that the mechanical stability can be used as a promising and an efficient alternative to computationally highly demanding estimation of binding affinity. However, mechanical stability defined as a peak in force-extension profile depends on the choice of the pulling direction. Here we propose an uncommon choice of the pulling direction along resultant dipole moment vector, which has not been explored in simulations so far. Using explicit solvent all-atom MD simulations, we apply steered molecular dynamics technique to probe mechanical resistance of protein-peptide system pulled along two different vectors. A novel pulling direction, along the resultant dipole moment vector, results in stronger forces compared to commonly used peptide unbinding along center of masses vector. Our results demonstrate that resultant dipole moment is one of the factors influencing the mechanical stability of protein-peptide complex.