Coarse-grained modeling of hydrodynamic behavior in DNA synthesis monomers

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.