Tight junctions (TJs) are the major barrier of paracellular permeation and modulate conventionally impenetrable barriers toward absorption, for example, the blood brain barrier (BBB) that blocks 98% of small molecule drugs). Our group is interested in studying the mechanism of TJs to design molecules that can pass the BBB.
Permeation enhancers (PEs) are a class of molecules that interact with the epithelial membrane and transiently increase its transcellular permeability to small molecule drugs. Recent experiments have shown that PEs can even enhances the passive permeation of small peptides. Our group is interested in understanding the structure-function relation of the PEs in enhancing permeation.
Read moreThere are several simplifications made in MD-based membrane simulations, which contribute to their discrepancy with the experiments. Simulations often employ homogeneous lipid bilayers, overlook the resistance from the unstirred water layer (UWL), and fix the protonation state of the permeant. Our group is interested in developing methods to model these factors to obtain a more reliable estimate of the permeability.
Read moreMembrane curvature has been shown to actively modulate various properties of the cellular membrane. Synaptic vesicles (SVs) are small, spherical compartments within nerve cells that store and release neurotransmitters at the synapse. SVs are highly curved and their association with mutated alpha-synuclein is linked with neurodegenerative disease like Parkinson's disease. Our group is interested in modeling highly curved membrane and laying the foundation of understanding its interaction with alpha-synuclein.
Read more