Molecular dynamics simulation of human urea transporter B

Abstract

ABSTRACT We applied a new large two membrane model of human urea transporter B (UT-B) with urea concentration gradient between intracellular and extracellular solution to explore the structure and dynamics of urea permeation. The first solved human UT-B X-ray crystal structure (PDB 6QD5) was studied using atomistic force field based large scale molecular dynamics (MD) simulations. The urea binding sites in UT-B were identified by the combination of first principles molecular dynamics docking and hybrid steered molecular dynamics (hSMD). In the simulations, urea molecules bound to the two binding sites although urea molecules did not go through the channels. The potential of mean force (PMF) of urea along the channel was calculated by hSMD to investigate the selectivity of the urea permeation across the channel pore. The simulations provide an opportunity to explore the binding sites spontaneously to help understand the urea permeation gating and transportation mechanism. A clearer analysis of the selectivity filter is shown in more detail. We also furthered the research about small organic molecules in the specific environment, such as channels in this work.