Document Type


Original Publication Date


Journal/Book/Conference Title

Biophysical Journal





First Page


DOI of Original Publication



Originally published at:

Under an Elsevier user license.

Date of Submission

January 2015


The slow delayed rectifier (IKs) channel is composed of KCNQ1 (pore-forming) and KCNE1 (auxiliary) subunits, and functions as a repolarization reserve in the human heart. Design of IKs-targeting anti-arrhythmic drugs requires detailed three-dimensional structures of the KCNQ1/KCNE1 complex, a task made possible by Kv channel crystal structures (templates for KCNQ1 homology-modeling) and KCNE1 NMR structures. Our goal was to build KCNQ1/KCNE1 models and extract mechanistic information about their interactions by molecular-dynamics simulations in an explicit lipid/solvent environment. We validated our models by confirming two sets of model-generated predictions that were independent from the spatial restraints used in model-building. Detailed analysis of the molecular-dynamics trajectories revealed previously unrecognized KCNQ1/KCNE1 interactions, whose relevance in IKs channel function was confirmed by voltage-clamp experiments. Our models and analyses suggest three mechanisms by which KCNE1 slows KCNQ1 activation: by promoting S6 bending at the Pro hinge that closes the activation gate; by promoting a downward movement of gating charge on S4; and by establishing a network of electrostatic interactions with KCNQ1 on the extracellular surface that stabilizes the channel in a pre-open activated state. Our data also suggest how KCNE1 may affect the KCNQ1 pore conductance.


From The Biophysical Journal, Xu,Y., Wang, Y., Meng, XY et al., Building KCNQ1/KCNE1 Channel Models and Probing their Interactions by Molecular-Dynamics Simulations, Vol. 105, Page 2461. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. Reprinted with permission.

Is Part Of

VCU Physiology and Biophysics Publications

mmc1 (1).pdf (5878 kB)
Three tables, thirteen (13) figures, and additional supplemental information.

mmc2.mp4 (42553 kB)
KCNE1 docking-induced conformational changes in the KCNQ1 peptide backbone based on principal component analysis.