Coarse-grained modeling of hydrodynamic behavior in DNA synthesis monomers

Abstract

Efficient DNA synthesis is crucial for advancements in DNA data storage and synthetic biology, yet the micro-scale dynamics of nucleotide monomers in solution, particularly their diffusion, are not fully understood. Here, we present a novel four-bead coarse-grained (CG) model for DMT (dimethoxytrityl)-protected nucleotide monomers, meticulously validated via Boltzmann inversion. This CG approach dramatically enhances computational efficiency (≥20×) compared to all-atom models, thus enabling simulations on significantly larger spatiotemporal scales. Using the stochastic Eulerian Lagrangian method to accurately model fluid–solid interactions, our simulations in acetonitrile reveal that monomer diffusion significantly decreases with increasing concentration due to enhanced intermolecular interactions. Channel walls impose substantial, concentration-dependent restrictions, especially perpendicular to the wall. Crucially, adenine and thymine monomers diffuse slower than cytosine and guanine monomers, providing a kinetic basis for variations in mass transfer efficiency during DNA synthesis. This study offers a new perspective for profoundly understanding the micro-dynamics during DNA synthesis, providing a potential way for optimizing synthesis parameters and advancing DNA data storage technology.