Macromolecular crowding and heterodimers formation

L.G. LÓPEZ

Buenos Aires

Workshop; Giambiagi Winter School XV; 2013

The inside of the living cell is highly crowded with macromolecules. These crowding agents significantly alter the motions (kinetics) and the stability (thermodynamics) of the encounter complexes. Today, there is a lot of literature about this phenomenon. However, little has been said about the effects of the environmental structuring on the complexes formation. Therefore, a simple modeling of structured environments is a first step towards more realistic simulations. In this work, using Monte Carlo simulations in continuous spaces, the effects (kinetics and thermodynamics) of macromolecular crowding on the formation of heterodimers were studied. For this, a model of hard disks in two dimensions was developed. The system is composed of three kinds of particles: “A” monomers, “B” monomers and “C” crowding agents (red, yellow, and grey particles respectively in Figure 1). Monomers A and B can form heterodimers AB (white arrows) through attractive patch-patch interactions, while “C” particles only present steric interactions. The test results were consistent with the results (theoretical, experimental and computational) reported in the literature. On this basis, several modifications were made to study the impact of the structure of the environmental crowding on the formation of AB heterodimers. Crowding agents can be mobile or immobile, monodisperse or polydisperse. On the other hand, these can form aggregates through attractive isotropic interactions, or worms (chains) through anisotropic interactions. The effects of these structures on the formation of heterodimers were analyzed.