Influence of Macromolecular Crowding on Protein-Protein Association Rates—a Brownian Dynamics Study

摘要

The high total concentration of macromolecules, often referred to as macromolecular crowding, is one of the characteristic features of living cells. Macromolecular crowding influences interactions between many types of macromolecules, with consequent effects on, among others, the rates of reactions occurring in the cell. Simulations to study the influence of crowding on macromolecular association rate were performed using a modified Brownian dynamics protocol. The calculated values of the time-dependent self-diffusion coefficients in different crowding conditions are in a very good agreement with those obtained by other authors. Simulations of the complex formation between the monoclonal antibody HyHEL-5 and its antigen hen egg lysozyme, both represented at atomic level detail, show that the calculated association rates strongly depend on the volume excluded by crowding. The rate obtained for the highest concentration of crowding particles is greater than twofold higher than the rate for proteins without crowding.