Molecular dynamics (MD) simulations model conformational dynamics and interactions between macromolecules with high-resolution but at a high computational cost. By combining high-throughput MD with statistical inference, it is now possible to obtain Markov state models (MSMs) of the long-time kinetics of small to intermediate biomolecules and complexes. To explore the behavior of molecules at large lengthscales, such as in cellular signal transduction, reaction-diffusion (RD) methods such as particle-based RD are more suitable. Thus, coupling MSMs and RD simulations (MSM-RD) would be highly desirable, as they could efficiently produce simulations at large time- and lengthscales, while still conserving the characteristic features of the interactions observed at molecular resolution. In this talk, we make a step towards MSM-RD by laying out a general theory of coupling and proposing a first implementation for association/dissociation of proteins with small ligands or substrates.
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