Perturbation
of Fluid Dynamics Properties of Water
Molecules during G Protein-Coupled Receptor–Ligand Recognition:
The Human A<sub>2A</sub> Adenosine Receptor as a Key Study
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Abstract
Recent
advances in structural biology revealed that water molecules
play a crucial structural role in the protein architecture and ligand
binding of G protein-coupled receptors. In this work, we present an
alternative approach to monitor the time-dependent organization of
water molecules during the final stage of the ligand–receptor
recognition process by means of membrane molecular dynamics simulations.
We inspect the variation of fluid dynamics properties of water molecules
upon ligand binding with the aim to correlate the results with the
binding affinities. The outcomes of this analysis are transferred
into a bidimensional graph called water fluid dynamics maps, that
allow a fast graphical identification of protein “hot-spots”
characterized by peculiar shape and electrostatic properties that
can play a critical role in ligand binding. We hopefully believe that
the proposed approach might represent a valuable tool for structure-based
drug discovery that can be extended to cases where crystal structures
are not yet available, or have not been solved at high resolution