Epitope Identification, A Case Study: Nanobodies Binding to mGluR5 Receptor
Schizophrenia is a mental disorder that affects approximately 1% of the worldwide population. Scientists finally developed a hypothesis that may interpret the pathophysiology behind this disorder, which is related to the deficiency of glutamate in the brain. Amongst glutamate targets, in this study we have focused on metabotropic glutamate receptor 5 (mGlu5). Due to the highly conserved orthosteric binding site of mGlu receptor subtypes, scientists developed an alternative approach to target mGluRs using nanobodies as allosteric modulators. A nanobody is defined as the variable fragment of the heavy chain-only antibody. Its small size and stability under extreme physical conditions make it an interesting therapeutic agent. In the present study, based on biological data stating that nanobody Nb5A acts as a positive allosteric modulator of rat mGlu5, we performed an epitope identification of Nb5A at mGlu5 receptor using molecular modeling techniques like docking and molecular dynamics and artificial intelligence algorithms. Two poses resulting from the docking of Nb5A to the active conformation of rat mGlu5 receptor were selected. Then, among the 2 poses, one was confirmed experimentally.
