A Brief View of Molecular Modeling Approaches to P2 Receptors

Abstract

Purinergic receptors are a class of receptors distributed into two groups, P1 and P2. P1 receptors are activated by nucleosides, like adenosine, while nucleotides active P2 receptors. In turn, P2 receptors comprise two families, metabotropic P2Y and ionotropic P2X. P2Y receptors consist in eight members, namely, P2Y1, P2Y2, P2Y4, P2Y6, P2Y11, P2Y12, P2Y13, and P2Y14, described in mammals, while P2X includes seven members, numbered P2X1 to P2X7. These receptors have been described as expressed in practically all cells studied to date. In this context, P2 receptors are suggested as participating in certain diseases. The general approach applied in the discovery of new drugs is expensive and lengthy. Alternatively, in the last 20 years, molecular modeling has emerged as an exciting tool for the design of new drugs, in less time and at low costs. These tools allow for in silico testing of thousands of molecules against a target protein, as well as toxicity, absorption, distribution, metabolism, and constant affinity predictions of a given interaction. Thus, molecular modeling algorithms emerge as an increasingly important tool for the design of drugs targeting purinergic receptors as therapeutic targets of many diseases, including cancer, pain, inflammation, cardiovascular, and endocrine conditions.

Purinergic receptors modulators: An emerging pharmacological tool for disease management

“…These homology models were used to study the P2X receptors whose crystal structures are not yet being solved. 326,327 7 | CONCLUDING REMARKS receptors, and only a few for P2YRs but findings of P2XRs ligands are still in nascent phases. This area of research still requires much more attention that will pay developed mechanistic approaches for the treatment of various life-threatening human diseases.…”

“…Along with crystal structures, various homology models for P2X receptor subtypes have also been developed based on the X‐ray structure of zebrafish P2X4 receptors. These homology models were used to study the P2X receptors whose crystal structures are not yet being solved 326,327 …”