1 research outputs found
Multiple Fragment Docking and Linking in Primary and Secondary Pockets of Dopamine Receptors
A sequential docking methodology
was applied to computationally
predict starting points for fragment linking using the human dopamine
D<sub>3</sub> receptor crystal structure and a human dopamine D<sub>2</sub> receptor homology model. Two focused fragment libraries were
docked in the primary and secondary binding sites, and best fragment
combinations were enumerated. Similar top scoring fragments were found
for the primary site, while secondary site fragments were predicted
to convey selectivity. Three linked compounds were synthesized that
had 9-, 39-, and 55-fold selectivity in favor of D<sub>3</sub> and
the subtype selectivity of the compounds was assessed on a structural
basis