Defense Date

11-16-2012

Graduation Date

2012

Availability

Immediate Access

Submission Type

thesis

Degree Name

MS

Department

Chemistry and Biochemistry

School

Bayer School of Natural and Environmental Sciences

Committee Chair

Jeffry D Madura

Committee Member

Michael Cascio

Committee Member

Jeffrey D Evanseck

Keywords

Biophysics, Modeling, Molecular Dynamics, Neurotransmitter, Transporters

Abstract

The solute carrier family regulates the flow of various substances such as drugs, amino acids, sugars and inorganic ions across the cell membrane. In particular, the monoamine transporters (MATs) are responsible for the regulation of synaptic neurotransmitter levels. Their structures and conformational rearrangements associated with transport remain unsolved. We employed novel computational techniques to identify the binding pocket of cocaine in the dopamine transporter (DAT) and two intracellular pathways for substrate egress in LeuT and DAT. We review possible coarse grained molecular dynamics techniques to extend the temporal scale accessible in simulations of the MATs. Finally, we present the first computational study of DAT in the presence of an explicit electrochemical gradient. In these simulations, we identify a water wire in DAT that may suggest that DAT does not follow an alternating access mechanism.

Format

PDF

Language

English

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