Molecular Mechanisms in the Function of Neurotransmitter Transporters: Multi-scale Computational Studies on Membrane Proteins

In my Ph. D. research work, I investigate functional mechanisms of complex molecular machines in the cell membrane that carry out the transport (reuptake) of neurotransmitter molecules into the cell. I apply and develop methods of computational biophysics to reveal and quantify the molecular transport process that is essential for the ability of the cell to continue to signal. Such detailed understanding is highly significant because dysfunction of these transporter proteins is known to be involved in neurodegenerative diseases, depression, epilepsy and stroke. The molecular mechanistic insights gained on multiple scales from my research work pertain to (1) a major conformational transition in the substrate translocation mechanism of Glutamate Transporters, and (2) allosteric changes in the substrate transport mechanism of the Neurotransmitter: Sodium Symporter proteins. The computational approaches that enabled these mechanistic insights include Motion Planning, mixed Elastic Network Models, (targeted) Molecular Dynamics Simulations, Free Energy Perturbations, and various statistical analysis methods.