MSM/RD: Coupling Markov state models of molecular kinetics with reaction-diffusion simulations

Area of Science:

• Computational biology
• Biophysics
• Chemical kinetics

Background:

• Molecular dynamics (MD) simulations offer high resolution but are computationally expensive.
• Markov state models (MSMs) extend timescale access for biomolecular dynamics.
• Particle-based reaction-diffusion (RD) simulations model large-scale systems but lack molecular detail.

Purpose of the Study:

• To develop a hybrid simulation approach coupling MSMs and RD (MSM/RD).
• To address fundamental questions regarding state definition and particle handling in coupled simulations.
• To enable efficient, large-scale, and detailed modeling of molecular interactions.

Main Methods:

• Laid out a general theory for coupling MSMs and RD simulations.
• Proposed an implementation for association/dissociation reactions (A + B ⇌ C).
• Applied the method to a toy model and CO diffusion into myoglobin.

Main Results:

• Demonstrated the feasibility of the MSM/RD coupling approach.
• Provided a framework for defining MSM states and handling particle merging/splitting.
• Successfully modeled CO diffusion into myoglobin using the new method.

Conclusions:

• The developed MSM/RD framework is a significant step towards bridging molecular detail and large-scale simulations.
• This hybrid approach offers a powerful tool for studying complex biological processes.
• Future work will refine the theory and expand applications to more intricate systems.