Comparing structural dynamic properties of diseases causing mutations of KCNE3 with wild-type KCNE3 in a lipid bilayer membrane using molecular dynamics simulations.

Abstract

KCNE3 is a potassium channel accessory transmembrane protein that regulates the function of various voltage-gated potassium channels such as KCNQ1 and KCNQ4. KCNE3 plays an important role in the recycling of potassium ion by binding with KCNQ1. KCNE3 can be found in the small intestine, colon, and in the human heart. Its malfunction has been proven to lead to disorders such as cardiac arrhythmia, long QT syndrome, tinnitus, cystic fibrosis, and Menière's disease. Despite of its biological significance, little is known about its structural and dynamic properties. Molecular dynamics (MD) simulation serves as a computational tool to study structural and dynamic properties of membrane proteins at an atomic level. Previously, we have studied structural and dynamic properties of wild-type KCNE3 in various lipid bilayer membranes. In this study, we have utilized all atom molecular dynamics simulation to investigate the structural dynamics of various disease causing mutations of KCNE3 in POPC/POPG lipid bilayers. The root mean square deviation (RMSD) of the different section of various diseases causing mutations of KCNE3 is compared to the wild-type KCNE3 to determine the changes in dynamic behavior. Our simulation results are consistent with electron paramagnetic resonance (EPR) experimental results.