A Charge Moving Algorithm for Molecular Dynamics Simulations of Gas-Phase Proteins

Area of Science:

• Computational biophysics
• Molecular dynamics simulations

Background:

• Understanding protein complex dissociation mechanisms is vital for interpreting experimental data like mass spectra.
• Gas-phase protein studies require methods that account for charge behavior.

Purpose of the Study:

• To develop and apply a Monte Carlo method for simulating charge movement in coarse-grained protein simulations.
• To investigate the role of charge movement in the dissociation and unfolding of protein complexes.
• To correlate simulation results with experimental observations from Collision-Induced Dissociation (CID) studies.

Main Methods:

• A Monte Carlo approach was developed to simulate charge hopping between sites in coarse-grained protein models.
• The algorithm was implemented within the GROMACS molecular dynamics software package.
• Transthyretin (TTR) tetramer using the MARTINI force field served as the model system for analysis.

Main Results:

• Charge movement significantly influences the unfolding mechanism of protein complexes.
• Analysis of energy distributions and pair correlation plots revealed insights into the charge hopping process.
• Hopping rates, charge distributions, and structural parameters (radius of gyration, RMSD) were calculated.
• Coulomb repulsion between charges was identified as the primary driver for charge hopping and unfolding.

Conclusions:

• Simulated charge movement is essential for accurately modeling protein complex dissociation.
• The developed Monte Carlo method provides a valuable tool for studying gas-phase protein dynamics.
• Coulomb repulsion plays a critical role in controlling protein complex unfolding and dissociation pathways.