The bacterial leucine transporter LeuT retains significant secondary structure similarities to the human monoamine transporters (MAT) such as the dopamine and serotonin reuptake proteins. As the MATs have not been crystallized, the primary method of computational modeling has been through the use of the crystallized LeuT structure. Different conformations of LeuT can give insight into mechanistic details of the MAT family. Previous work on LeuT was a conformational sampling performed through several accelerated molecular dynamics (aMD) simulations testing different combinations of the leucine substrate and bound sodium ions. Initial analysis of the trajectories was performed using principal component analysis, and seven distinct conformational clusters were found. Further analysis has been performed to target certain residues and transmembrane domains on both the seven isolated structures and the total trajectories. In addition, solvent accessibility of LeuT and its substrate binding pockets has been analyzed using a program for calculating channel radii.

Analysis of structural dynamics from a conformational sampling of the bacterial monoamine transporter homologue LeuT

243rd National Meeting (2012)

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