The association of KCNE3 (E3) with KCNQ1 (Q1) forms KCNE3/KCNQ1 channels that are voltage-independent within the physiological voltage range. This is crucial for cardiac action potentials and water and salts transport in epithelial cells. Transmembrane domain (TMD) of KCNE3 interacts with KCNQ1 to lock its voltage sensor in a depolarized conformation, critical for controlling Q1 voltage dependence. Despite the biological significance, details of specific TMD sites responsible for this stabilization remain unclear. Computational techniques, such as molecular dynamics (MD) simulations, are powerful tools for investigating the stability, dynamics, and conformational changes of membrane proteins and their interactions. In this project, a 200 ns all-atom molecular dynamics simulations performed on KCNE3/KCNQ1 complex embedded within the POPC/POPG lipid bilayer membrane using Nano-scale molecular dynamics (NAMD) is used to study conformational dynamics of E3 TMD while interacting with KCNQ1. ClusPro 2.0 server was employed during the molecular docking between E3 and Q1 to obtain E3/Q1 complex. CHARMM-GUI is used for simulation set up and input generation and visual molecular dynamics (VMD) is used for MD trajectory analysis. Simulation trajectory data were analyzed to determine various conformational dynamics-related parameters, including backbone root mean square deviation (RMSD), root mean square fluctuation (RMSF), TMD helical bending angle, protein-protein interaction energy, contact analysis, percentage hydrogen bond occupancy, community network analysis, and principal component analysis (PCA). Differences in the conformational dynamics of KCNE3 TMD upon interaction with KCNQ1 were revealed by comparing these results obtained for the KCNE3/KCNQ1 complex and for the KCNE3 alone. This study will complement ongoing biophysical investigations of the KCNE3/KCNQ1 complex in lipid bilayers.
Sahu et al. (Sun,) studied this question.