Multiscale molecular kinetics by coupling Markov state models and reaction-diffusion dynamics.

Area of Science:

• Computational Chemistry
• Biophysics
• Molecular Dynamics

Background:

• Simulating molecular interactions at large scales is computationally challenging.
• Existing Markov state models (MSMs) coupled with reaction-diffusion (RD) simulations (MSM/RD) have limitations in mathematical framework, ligand isotropy, and multiparticle extensions.

Purpose of the Study:

• To develop a general MSM/RD framework addressing current limitations.
• To enable accurate modeling of protein-protein interactions and multiparticle systems at large time and length scales.

Main Methods:

• Coarse-graining molecular dynamics into hybrid switching diffusion processes.
• Developing a mathematical framework for MSM/RD coupling schemes.
• Implementing and verifying the framework for protein-protein interactions and multiparticle systems.

Main Results:

• A generalized MSM/RD framework capable of modeling protein-protein interactions over large scales.
• Successful extension to handle multiple interacting molecules.
• Verified framework performance on benchmark systems and modeling pentameric ring formation.

Conclusions:

• The developed MSM/RD framework provides a robust and extensible method for simulating complex molecular systems.
• The published software package ensures reproducibility and facilitates further research in computational biophysics.