Research Repository

New insights into key determinants for adenosine 1 receptor antagonists selectivity using supervised molecular dynamics simulations

Bolcato, Giovanni and Bissaro, Maicol and Deganutti, Giuseppe and Sturlese, Mattia and Moro, Stefano (2020) 'New insights into key determinants for adenosine 1 receptor antagonists selectivity using supervised molecular dynamics simulations.' Biomolecules, 10 (5). ISSN 2218-273X

[img]
Preview
Text
biomolecules-10-00732.pdf - Published Version
Available under License Creative Commons Attribution.

Download (2MB) | Preview

Abstract

Adenosine receptors (ARs), like many otherGprotein-coupledreceptors (GPCRs), are targets of primary interest indrug design. However, one of the main limits for the development of drugs for this class of GPCRs is the complex selectivity profile usually displayed by ligands. Numerous efforts have been madefor clarifying the selectivity of ARs, leading to the development of many ligand-based models. The structure of the AR subtype A1 (A1AR) has been recently solved,providing important structural insights. In the present work, we rationalized the selectivity profile of two selective A1AR and A2AAR antagonists, investigating their recognition trajectories obtained by Supervised Molecular Dynamics from an unbound state and monitoring the role of the water molecules in the binding site.

Item Type: Article
Additional Information: This article belongs to the Special Issue In Silico Drug Design for GPCRs: Big Data for Small Molecule Discovery
Divisions: Faculty of Science and Health > Life Sciences, School of
Depositing User: Elements
Date Deposited: 21 May 2020 15:03
Last Modified: 21 May 2020 15:03
URI: http://repository.essex.ac.uk/id/eprint/27590

Actions (login required)

View Item View Item