Multiscale Brownian dynamics simulations reveal effects of macromolecular crowding on protein-ligand association.

Macromolecular crowding in Brownian dynamics simulations is linked to both hindered and enhanced bimolecular association rates for protein–small molecule inhibitor complexes, depending on crowder type and density.

• Why it matters: Quantitative predictions of how crowding alters protein–small molecule binding kinetics are limited, despite its known effects on diffusion, binding, and equilibrium in cells and concentrated therapeutic solutions.
• What they did: An adaptive multiscale Brownian dynamics model was implemented in SDA, combining atomistic short-range and coarse-grained long-range crowder interactions, then used with Markov State modeling of encounter trajectories.
• The result: Crowders can reduce translational diffusion and obstruct binding sites, yet they can also increase association rates via channeling and the caging effect in the simulated inhibitor–protein environments.

AI summary of the abstract · may contain errors · not medical advice · read the paper.