Accelerating Steered Molecular Dynamics: Toward Smaller Velocities in Forced Unfolding Simulations

Area of Science:

• Computational biophysics
• Protein dynamics simulation

Background:

• Steered molecular dynamics (SMD) is the standard for simulating protein forced unfolding.
• Accurate simulation of protein unfolding requires proper equilibration of the protein-solvent system.

Purpose of the Study:

• To introduce and validate a hybrid accelerated molecular dynamics (aMD) and SMD scheme for protein unfolding simulations.
• To assess the impact of enhanced sampling on the accuracy of force-distance curves.

Main Methods:

• A hybrid simulation approach combining aMD and SMD was implemented.
• Simulations focused on forced protein unfolding experiments.
• Analysis centered on force-distance curves and system equilibration.

Main Results:

• The hybrid aMD-SMD scheme alters force-distance curves, particularly near the force maximum.
• Improved equilibration of the protein-solvent system was observed with the hybrid method.
• Simulations using the hybrid scheme show better agreement with experimental data.

Conclusions:

• The hybrid aMD-SMD method offers a more accurate approach for simulating protein forced unfolding.
• Enhanced sampling via aMD improves the comparability of simulations to experimental results.
• This hybrid scheme is valuable for studying protein mechanical properties.