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204 Biomolecular diffusional association Razif R Gabdoulline and Rebecca C Wade* The primary method for the computational study of fasciculin to acetylcholinesterase, and binding of the biomolecular diffusional association is Brownian dynamics. intracellular inhibitor barstar to the extracellular ribonuclease Recent work has seen advances in the efficiency of barnase. Some enzymes, for example, acetylcholinesterase computing association rates and in the accuracy of simulation and superoxide dismutase (SOD), have such optimised models. New areas to which Brownian dynamics has been chemical steps that their rates are limited by diffusion. applied include protein polymerisation and protein adsorption to a surface. There has recently been particularly intense Although the relevance of diffusion in in vitro biochemical study of protein–protein association, and Brownian dynamics, experiments in dilute solution is clear, its relevance in the together with other theoretical and experimental approaches, crowded cellular environment in vivo is sometimes queried. has led to new insights into the determinants of Many macromolecules are relatively immobilised in protein–protein binding kinetics. membranes, some can only move in the confined spaces of certain organelles and active transport mechanisms exist. But Addresses simulations of diffusional association are not just relevant to European Media Laboratory (EML) and European Molecular Biology extracellular diffusion. Inside the cytoplasm, experiments Laboratory (EMBL), Heidelberg, Germany indicate that, for molecules up to