Computational Analysis of Protein-Protein Interactions of G Protein Coupled Receptors

Abstract

Background & Objective: Chemokine (C-C motif) receptor 7 (CCR7) is a class A subtype G-Protein Coupled
Receptor. It contributes to the migration and activation of dendritic cells, T cells, eosinophils, B cells and different
cancer cells. CCR7 signalling system is involved in T cell activation, immune tolerance, inflammatory response and
cancer metastasis. CCL19 and CCL21 are the two CCR7 ligands and are differential in their signalling through
CCR7. Methodology: The sequence of the ligand and the receptor has been extracted from GPCR database to
understand the signalling system. The interacting 3D structure of CCR7-CCL19 and CCR7-CCL19 has been studied
with 3did the database of three dimensional interacting domains (3did) to know the domain interaction. The
interaction networks of GPCR and the ligands have been studied with STRING, an interaction database. The GPCR
and the ligands have been modelled using Swiss Model. The network of the differential signalling of CCL19 and
CCL21 with CCR7 has been visualized with the help of NetSlim. The modelled CCR7 were further docked with
CCL19 and CCR7 in Hex. Results: The network was obtained for CCR7 pathway and the maximum score for the
interaction between CCR7 and CCL19 was found to be 0.999 and the maximum score for interaction between CCR7
and CCL21 was found to be 0.999. The interaction between CCR7 and CCL19 is between chain A and chain C of
7tm_1 (CCR7) and IL8 (CCL19). The modelled CCR7 was docked against the two ligands CCL19 and CCL21 and
the energy for the interaction between CCR7 and CCL19 was 477 units where as the energy for interaction between
CCR7 and CCL21 was 452.38 units. This shows that the two ligands bind differentially to CCR7. showed significant
inhibition with minimum binding energy, when compare to standard drug ciprofloxacin and amphotericin B.
Conclusion: This study clearly showed that the amentoflavone used as broad spectrum of antimicrobial drug.