American Chemical Society
ct6b00475_si_008.pdb (377.28 kB)

Probing Hydration Patterns in Class‑A GPCRs via Biased MD: The A2A Receptor

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posted on 2016-11-10, 20:34 authored by Syeda Rehana Zia, Roberto Gaspari, Sergio Decherchi, Walter Rocchia
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 A2A receptor, a target of significant pharmaceutical relevance. The results of the approach are enriched with an extensive analysis of hydration in A2A and 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.