The Scatchard plot analysis demonstrates that two classes of binding sites are formed with the equilibrium dissociation constants.
One of those additional binding sites is formed by the region around Cys60 (which is the cysteine responsible for the dimerization (see above), and it is the predicted interaction site with NTR [71]); furthermore, the majority of those other four additional sites involve the hydrophobic side chains of several lysine residues present in PsTRXf and not in the other two proteins (Fig. 1).
The 5-HT3 receptor belongs to a family of therapeutically important neurotransmitter-gated receptors whose ligand binding sites are formed by the convergence of six peptide loops (A-F).
In particular, the long-held belief that agonist binding sites are formed only at α interfaces has been challenged by increasing evidence for a viable agonist binding site at α interfaces.
Uniquely among the family of glutamate ionotropic receptors, NMDA receptors require both glutamate and glycine (a co-agonist) to bind to the receptor for channel activation to occur with the glycine binding site being formed by the S1 and S2 domains of the GluN1 subunit and glutamate binding site being formed from the homologous regions on the GluN2 subunit.
Finally, a third method of incorporating pharmacophores into virtual screening is to add constraints to the docking run to ensure that certain interactions between the ligands and the target binding site are formed.
Even though this binding site is formed by residues of helices H3, H4 and H12, its conformation is mainly determined by the H12 position.
