Abstract
Molecular machinery is capable of many tasks using few components. Some systems assemble machinery to accelerate chemical reactions, while others assemble to provide scaffolding. Here we will examine several systems of machinery and their components to better understand what factors can be used to predict machine behavior. First, we describe dynamical simulations of the assembly of an icosahedral protein shell around a bicomponent fluid cargo. Our simulations are motivated by the goal of designing synthetic bacterial microcompartments - protein shells found in bacteria. These microcompartments assemble around a complex of enzymes and their reactants involved in certain metabolic processes. The simulations demonstrate that the relative interaction strengths among the different cargo species play a key role in determining the amount of each encapsulated species, their spatial organization, and the nature of the shell assembly pathways. However, the shell protein-protein and shell-cargo interactions that help drive assembly and encapsulation also influence cargo composition within certain parameter regimes. These behaviors are governed by combination of thermodynamic and kinetic effects. In addition to elucidating how natural microcompartments encapsulate multiple components involved within reaction cascades, these results have implications for synthetic biology efforts to colocalize alternative sets of molecules within microcompartments to accelerate reactions. More broadly, the results suggest that coupling between self-assembly and multicomponent liquid-liquid phase separation may play a role in organization of the cellular cytoplasm. Next, we examine simulations of microtubules with crosslinkers and motors. These simulations are based on microtubule filaments that span the cell acting as part of the cytoskeleton. The vimotors and crosslinkers provide rigidity and activity to the simulations, creating different resulting filament networks. We determined the relative quantities of components needed for targeted levels of activity and elasticity. These results aid active network research by furthering understanding of rational design of the network. Finally, we develop a framework of carboxysome hexamer multiscale simulations. Carboxysomes are a type of bacterial microcompartment whose shell is comprised of hexameric and pentameric subunits, used to accelerate the Calvin cycle. The simulations compare hexameric interactions at different scales helping to clarify both the all-atom interaction geometry and the effect that it has on a larger scale. Using these comparisons, large scale simulations of a rigid body approximation of a hexameric subunit will improve our understanding of the behavior of the assembling subunits.