Computational studies of molecular permeation through large-pore channels.

Abstract

Connexin hemichannels are a family of highly regulated non-beta-barrel large-pore channels permeable to diverse small molecules. Despite their critical roles in mediating biological signaling, the molecular basis of selective permeation through these pores remains unclear. To bridge the knowledge gap between the structure and function of these large-pore channels, we use two complementary molecular dynamics (MD) simulation techniques, rare-event sampling and non-equilibrium steady-state flux, to compute the free energies and kinetics of molecular permeation through connexins. The link between these macroscopic properties and atomistic details of the permeation process provides valuable information for understanding the selectivity of large-pore channels and how human connexin mutations cause diseases.