DFT study of ligand binding in the β1 adrenergic receptor

Safarian, D., Simons, M., Evans, R. G., Peterson, L. W. and Cafiero, M. ORCID: https://orcid.org/0000-0002-4895-1783 (2021) DFT study of ligand binding in the β1 adrenergic receptor. Computational and Theoretical Chemistry, 1199. 113208. ISSN 2210271X doi: 10.1016/j.comptc.2021.113208

Abstract/Summary

The β2-adrenergic receptor, located in the prostate region, binds noradrenaline and can influence the growth of prostate tumors. The removal of Adrb2, the gene for this receptor, can halt tumor growth and thus can serve as an alternative to chemotherapy for cancer treatment. Inhibition of the receptor may have similar effects. Comparison of β2- (PDB ID: 5X7D) and β1-adrenergic receptor (PDB ID: 2Y04) structures showed a conserved binding region on Chain A offset by approximately eight amino acids between the two receptors. The structure of the β1-adrenergic receptor with the bound partial agonist salbutamol was used to create a model of the active site of the β2-adrenergic receptor. Potential inhibitors were optimized in the receptor binding site using M062X/6-31G with relaxed amino acid sidechains. Interaction energies between the ligands and the receptor were calculated using M062X/6-311+G*. Positively charged inhibitors show greater interaction energies as compared to negatively charged inhibitors.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/108191
Identification Number/DOI	10.1016/j.comptc.2021.113208
Refereed	Yes
Divisions	Life Sciences > School of Chemistry, Food and Pharmacy > Department of Chemistry
Publisher	Elsevier
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