Molecular Dynamic Simulations of Human Purinergic Receptor Subtype P2  × 7 Bonded to Potent Inhibitors.

Molecular Dynamic Simulations of Human Purinergic Receptor Subtype P2 × 7 Bonded to Potent Inhibitors. Eur J Pharm Sci. 2020 Jul 03;:105454 Authors: Santos EG, Faria RX, Rodrigues CR, Bello ML Abstract Among the members of purinergic receptors, the family P2X of ionotropic proteins has the ion channel subtype P2 × 7 that show in studies to be an important molecular target for new drugs. The activity of human P2 × 7 receptor (hP2 × 7r) in the body, due to its pro-inflammatory function, can trigger physiological disorders related to chronic inflammatory processes, leading to neural degeneration, neuropathic pain and chronic pain. Recently, two series of promising new inhibitors of the hP2 × 7r ion channel have been reported. One series consisted of naphthoquinone derivatives and the other composed of triazole derivatives. The main objective of this study was to understand the binding mode differences between the hit compounds of each series and compare them to the native ligand ATP. The hP2 × 7r ion channel and membrane lipid models were prepared in order to allow study the appropriate protein molecular dynamics. Molecular modeling and molecular dynamics simulation approaches were applied in order to obtain atomistic and molecular details that are involved in intermolecular interactions. Both compounds AN-04 and 9d seem to have affinity to binding in the hP2 × 7r pore area according to molecular dynam...
Source: European Journal of Pharmaceutical Sciences - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharm Sci Source Type: research