title: Insilico study of the A(2A)R-D          (2)R kinetics and interfacial contact surface for heteromerization.
abstract: G-protein-coupled receptors (GPCRs) are cell surface receptors. The dynamic property of receptor-receptor interactions in GPCRs modulates the kinetics of G-protein signaling and stability. In the present work, the structural and dynamic study of A(2A)R-D(2)R interactions was carried to acquire the understanding of the A(2A)R-D(2)R receptor activation and deactivation process, facilitating the design of novel drugs and therapeutic target for Parkinson's disease. The structure-based features (Alpha, Beta, SurfAlpha, and SurfBeta; GapIndex, Leakiness and Gap Volume) and slow mode model (ENM) facilitated the prediction of kinetics (K                         (off), K                         (on), and K                         (d)) of A(2A)R-D(2)R interactions. The results demonstrated the correlation coefficient 0.294 for K                         (d) and K                         (on) and the correlation coefficient 0.635 for K                         (d) and K                         (off), and indicated stable interfacial contacts in the formation of heterodimer. The coulombic interaction involving the C-terminal tails of the A(2A)R and intracellular loops (ICLs) of D(2)R led to the formation of interfacial contacts between A(2A)R-D(2)R. The properties of structural dynamics, ENM and KFC server-based hot-spot analysis illustrated the stoichiometry of A(2A)R-D(2)R contact interfaces as dimer. The propensity of amino acid residues involved in A(2A)R-D(2)R interaction revealed the presence of positively (R, H and K) and negatively (E and D) charged structural motif of TMs and ICL3 of A(2A)R and D(2)R at interface of dimer contact. Essentially, in silico structural and dynamic study of A(2A)R-D(2)R interactions will provide the basic understanding of the A(2A)R-D(2)R interfacial contact surface for activation and deactivation processes, and could be used as constructive model to recognize the protein-protein interactions in receptor assimilations.
authors.affiliation: Medicinal Chemistry Division, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, North Campus, Mall Road, Delhi, 110007, India.
authors.forename: Amresh
authors.initials: A
authors.lastname: Prakash
authors.forename: Pratibha Mehta
authors.initials: PM
authors.lastname: Luthra
mesh_terms: D000818:Animals; D003198:Computer Simulation; D005057:Eukaryotic Cells / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D051379:Mice; D008958:Models, Molecular; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D051381:Rats; D020239:Receptor Cross-Talk; D043705:Receptor, Adenosine A2A / Q000737:chemistry* / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000737:chemistry* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D043705:Receptor, Adenosine A2A; D017448:Receptors, Dopamine D2