(260a) Molecular Investigation into the Transport across the Blood-Brain Barrier Interface [Invited Talk]

The blood-brain barrier is an interfacial barrier constituted by claudin-5 membrane proteins. The selective permeability of chemical across this interfacial barrier is responsible for the lack of treatment options for neurodegenerative diseases such as Alzheimer’s and Parkinson’s. In an effort to overcome this hurdle, we use multiscale molecular simulations to study the intricate self-assembly of claudin-5 transmembrane proteins in explicit membrane and solvent environment. Based on the simulation we were able to identify the stable dimer conformations that result from membrane driven claudin-5 cis interactions and the corresponding pore structures. Our results reveal the nature of the molecular interactions that drive claudin-5 aggregation in forming the tight junctions, and are in good agreement with the previous experimental predictions. The insights from this study will help in designing the next generation of smart therapeutics that can permeate the blood-brain barrier interface.