Computational Modeling of Molecular Structure, Assembly, and Dynamics at Nanoscale

Today, atomic simulations of biological systems and materials can reach unprecedented scales, providing in-depth insight into the structural and dynamic properties of a system of particles governed by classical equations of motion. In two main projects, the studies presented in this dissertation employ molecular dynamics simulations to study the structural and physical properties of large-scale biological and chemical complexes over microsecond timescales. (i) In the first project, the macromolecular assembly and functional flexibility of the tight junctions claudins are studied. Tight junctions mediate the epithelial transport and are composed of a network of claudin channels that seal the space between two adjacent cells and control the transport of water and small molecules. Claudins polymerize to form a network of linear strands in the cell membrane that associates laterally with a similar network in adjoining cells. The architecture of claudin assemblies is flexible and therefore enables tight junctions to maintain their barrier function throughout cellular movements and tissue rearrangements. However, this flexibility’s molecular basis remains elusive. This thesis develops an atomic model of claudin-15 strands in two parallel lipid membranes at sub-micrometer length ranges. Microseconds-long molecular dynamic simulations of claudin-15 strands showcase the strands’ flexible nature and elucidate their flexibility’s molecular nature. Furthermore, to explain the subtype-specific morphology of claudin strands, the equilibrium behavior of wild-type and mutant claudin-15 strands are compared, validating the putative model of strand flexibility, as observed in simulation trajectories. (ii) The second project in this thesis investigates the phase behavior of ternary ionic liquid electrolyte mixtures. The performance and stability of battery electrolytes are, in part, the obstacles hindering the widespread usage of advanced and renewable energy storage systems, namely, lithium batteries. Recently, ternary mixtures of ionic liquid electrolytes have shown promising performance in Li-ion and Li-air batteries. However, the large-scale organization of the electrolyte mixture—beyond the local heterogeneities—that underpins the system’s dynamic properties is unexplored. In this thesis, microseconds-long molecular dynamics simulations reveal the formation of ion-enriched macrodomains in a ternary mixture of ionic liquid, organic solvent, and Li salts. Moreover, the mixtures’ phase behavior is examined in a confined space, similar to a cell battery configuration. The simulation trajectories elucidate the molecular basis of electrolytes’ phase separation, leading to better battery performance.