98
Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery Poster Session I
45-POS
Board 45
Modeling Multi-Protein Assembly Processes Using Single-Particle Reaction Diffusion
Margaret Johnson
.
Johns Hopkins University, Baltimore, MD, USA.
Biological processes ranging from receptor mediated signaling to clathrin-mediated endocytosis
depend on populations of distinct proteins competing and cooperating to stochastically form
protein complexes at the membrane and in solution. The recruitment of proteins to both the
membrane surface and to growing protein complexes can significantly alter a protein’s dynamics
and subsequent binding reactions. Building accurate models of these complex processes
therefore requires tracking both the spatial and temporal evolution of proteins and their higher
order assemblies. The challenge for these models lies in accurately reproducing experimentally
known reaction rates between protein domains while correctly accounting for multi-protein
complex formation at time scales of seconds or longer. We show how a recently developed
algorithm for efficient simulation of single-particle protein-protein interactions can be extended
to model protein recruitment and binding on the membrane, as well as specific protein-domain
interactions. This free-propagator reweighting (FPR) method combines simple position updates
to the proteins using free diffusion along with a trajectory reweighting method that allows us to
recover the correct association rates for all binding interactions. The method extends readily
from 3D solution to the 2D membrane, and the approach can correctly reproduce effects of
rotational motion and orientational contraints on protein-protein interactions. With this level of
spatial and structural resolution we are uniquely able to quantify the changes in protein binding
dynamics that occur upon membrane binding and complex formation. With an assembly process
such as occurs in the early stages of clathrin-mediated endocytosis, changes in the interaction
dynamics could provide important controls for the successful formation of the clathrin protein
coat, where protein motion is constrained by other proteins and by the membrane.
