title: Probing Hydration Patterns in Class-A GPCRs via Biased MD: The A2AReceptor.
abstract: Herein, we present a new computational approach for analyzing hydration patterns in biomolecular systems. This protocol aims to efficiently identify regions where structural waters may be located and, in the case of protein-ligand binding, where displacing one or more water molecules could be advantageous in terms of affinity and/or residence time. We validated our approach on the adenosine A2Areceptor, a target of significant pharmaceutical relevance. The results of the approach are enriched with an extensive analysis of hydration in A2Aand other members of the A-family of GPCRs using available crystallographic evidence and reviewing existing literature. As per the protein-ligand complex case, we conducted a more detailed study of a series of triazine analogues inhibiting A2A. The proposed approach provides results in good agreement with existing data and offers interpretability and simple and fast applicability.
authors.forename: Syeda Rehana
authors.initials: SR
authors.lastname: Zia
authors.forename: Roberto
authors.initials: R
authors.lastname: Gaspari
authors.affiliation: BiKi Technologies s.r.l. , Via XX Settembre, 33/10, I-16121 Genova, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Decherchi
authors.forename: Walter
authors.initials: W
authors.lastname: Rocchia
mesh_terms: D008024:Ligands; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D043705:Receptor, Adenosine A2A / Q000737:chemistry* / Q000378:metabolism; D013816:Thermodynamics; D014227:Triazines / Q000737:chemistry / Q000378:metabolism; D014867:Water / Q000737:chemistry
chemical_list: D008024:Ligands; D043705:Receptor, Adenosine A2A; D014227:Triazines; D014867:Water