Protein-Protein Association Free Energy From ReaDDY Simulation

Abstract

Simulating the conditions and various processes occuring inside a biological cell is still a formidable task due to the high concentration of macromolecules present. In a systematic approach to study the Protein-Protein association reactions in cellular conditions, a particle based simulation strategy is used. A Reaction Diffusion Dynamics method is employed using ReaDDy to simulate the diffusive behaviour of the proteins and crowders taken as spherical beads with size equal to their hydrodynamic radii. Harmonic repulsive and LennardJones interactions are given between the proteins and crowders to understand the effect of interactions on the free energy change of Protein-Protein associations in presence of crowders. Protein-Protein association reaction events can occur with certain rates, if they come within the reaction radius. Crowders are filled within the simulation box with different volume fractions upto 0.35 to simulate the physiologically relevent concentrations inside the cell. For a prolonged simulation of proteins and crowders, we observed many association and dissociation events. Free energy change of the association in presence of crowders is then obtained from the number of frames of the dimer state and the monomer state in presence and absence of crowders. Theoretical model such as Scaled particle theory is used to compare the results from the simulation. The observed simulation results for harmonic repulsive interaction agrees with the theoretical estimate.