Quantitative Structure-Activity Relationship Analysis of the Cation Permeability of the P2X2 Channel

Peter   P.   Mager; Anje      Weber; Peter      Illes

doi:10.2174/1573406053175210

Abstract

The membrane-embedded, ligand-gated P2X glycoprotein receptor is a monovalent-bivalent cation channel that is activated by physiological concentrations of extracellular ATP. A quantitative structure-activity relationship (QSAR) analysis was developed to model the cation permeability of the P2X2 channel and its mutants. As chemical properties, the helix-coil equilibrium constants and the distribution coefficients of the system octanol/water at pH 7.4 were applied and modified (sliding windows) according to Eroshkin et al. (Comput. Appl. Biosci., 1995, 11, 49-44). The results were visualized by a dimeric P2X2 channel construct. The results support the hypothesis that residues which put into the cavity and contribute to hydrogen bonding forces are involved to a control of the transport of hydrated cations through the P2X2 channel. The model may be useful to develop P2X2 receptor antagonists.

Keywords: molecular modelling, structural bioinformatics, quantitative structure-activity relationship, qsar, nonleastsquares regression analysis, p2x receptor, p2x2 receptor subunit, cation channel, calcium permeability, helix-coil equilibrium constant