Continuum electrostatic and free energy perturbation calculations on leucine transporter complexed with tricyclic antidepressants

COMP 224

Kalyan Immadisetty, immadisettyk@duq.edu, Jonathon D. Gibbons, gibbonsj@duq.edu, and Jeffry D. Madura. Department of Chemistry and Biochemistry, Center for Computational Sciences, Duquesne University, pittsburgh, PA 15282
Leucine transporter (LeuT) is a transmembrane protein belonging to neurotransmitter sodium symporter (NSS) family. Crystal structures of LeuT with tricyclic antidepressants, e.g. clomipramine, desipramine, and imipramine, have been recently reported. Free energy changes involved in the binding of these tricyclic antidepressants with the LeuT have been calculated using the continuum electrostatic method, and the relative free energy of binding for clomipramine to imipramine, imipramine to desipramine, and clomipramine to desipramine complexed with LeuT has been calculated using the free energy perturbation method (FEP). The continuum electrostatic and FEP results are in agreement with the experimental values.
 

Poster Session
6:00 PM-8:00 PM, Tuesday, August 18, 2009 Walter E. Washington Convention Center -- Ballroom A, Poster

Division of Computers in Chemistry

The 238th ACS National Meeting, Washington, DC, August 16-20, 2009