Force probe simulations using an adaptive resolution scheme

TL;DR

This paper introduces a hybrid multiscale simulation approach combining atomistic and coarse-grained models for force probe molecular dynamics, enabling efficient non-equilibrium biomolecular unfolding simulations.

Contribution

It demonstrates the application of the adaptive resolution scheme (AdResS) to non-equilibrium FPMD simulations, expanding its use beyond equilibrium scenarios.

Findings

Multiscale simulations match all-atom results for biomolecular unfolding.

The size of the atomistic region depends on pulling velocity.

Multiscale approach is effective in strong non-equilibrium conditions.

Abstract

Molecular simulations of the forced unfolding and refolding of biomolecules or molecular complexes allow to gain important kinetic, structural and thermodynamic information about the folding process and the underlying energy landscape. In force probe molecular dynamics (FPMD) simulations, one pulls one end of the molecule with a constant velocity in order to induce the relevant conformational transitions. Since the extended configuration of the system has to fit into the simulation box together with the solvent such simulations are very time consuming. Here, we apply a hybrid scheme in which the solute is treated with atomistic resolution and the solvent molecules far away from the solute are described in a coarse-grained manner. We use the adaptive resolution scheme (AdResS) that has very successfully been applied to various examples of equilibrium simulations. We perform FPMD simulations using AdResS on a well studied system, a dimer formed from mechanically interlocked calixarene capsules. The results of the multiscale simulations are compared to all-atom simulations of the identical system and we observe that the size of the region in which atomistic resolution is required depends on the pulling velocity, i.e. the particular non-equilibrium situation. For large pulling velocities a larger all atom region is required. Our results show that multiscale simulations can be applied also in the strong non-equilibrium situations that the system experiences in FPMD simulations.