Molecular dynamics studies of G protein-coupled Adenosine A2B receptor

Vol. 1, 2019 - 110435
Favoritar este trabalho
Como citar esse trabalho?

Currently, 60% of all drugs in the market bind to G-protein coupled receptors (GPCR)¹. Among GPCRs, adenosine-subtype A2B has raised interest because it is related to diseases such as cancer and sickle cell disease². However, this target doesn’t have a crystallographic structure available. Thus, we built the receptor 3D model on SWISS-Model server3(template PDB:5IU7; 60.26% identity) with adequate structural parameters: GMQE (0.75) and QMEAN(-3.12). Through CHARMM-GUI server, we inserted it into a lipid membrane and ran a molecular dynamics (MD) simulation on GROMACS 5.1.24: CHARMM forcefield; pH=7.4; NVT; T=303.15K; t=100ns. We compared the stability of our systems: A2B and A2B-antagonist. The deviation and fluctuation data were: 3.14x10-1± 5.81x10-2nm (A2B) and 1.61x10-1± 5.31x10-3nm (A2B-antagonist) and 1.11x10-1± 8.45x10-2nm (A2B) and 6.89x10-2± 2.61x10-2nm (A2B-antagonist). The antagonist stabilizes binding-site residues when compared to the A2B form, making the system reliable to be used in next virtual screening steps to identify new promising A2B antagonists.

Adenosine receptor
molecular dynamics
Homology modeling