Computational characterization of structural dynamics underlying function in active membrane transporters

By Jing Li, Po-Chao Wen, Mahmoud Moradi, and Emad Tajkhorshid.

Published in Curr Opin Struct Biol. 2015 Apr;31:96-105. Epub 2015 Apr 27.
PMID: 25913536. PMCID: PMC4476910 [Available on 2016-04-27]. Link to publication page.

Core: Computational Modeling Core.

Figure 1. Representative membrane transporters and functional events studied recently. Proteins are shown in cartoon representation, with the lipid bilayer in the background. Each transporter respectively represents a well-documented superfamily/family of membrane transporters in recent computational studies. Four close-up views of local conformations relevant with several critical functional events, that is, Na+-binding (left), H+-binding (middle left), ATP binding (middle right), and substrate binding (right).


Active transport of materials across the cellular membrane is one the most fundamental processes in biology. In order to accomplish this task, membrane transporters rely on a wide range of conformational changes spanning multiple time and size scales. These molecular events govern key functional aspects in membrane transporters, namely, coordinated gating motions underlying the alternating access mode of operation, and coupling of uphill transport of substrate to various sources of energy, for example, transmembrane electrochemical gradients and ATP binding and hydrolysis. Computational techniques such as molecular dynamics simulations and free energy calculations have equipped us with a powerful repertoire of biophysical tools offering unparalleled spatial and temporal resolutions that can effectively complement experimental methodologies, and therefore help fill the gap of knowledge in understanding the molecular basis of function in membrane transporters.


Figure 2. Monitoring water dynamics within proteins brings novel insights into transport mechanism.

Figure 3. Example of protein-lipid interactions captured in MD simulations.

Figure 4. Investigating the OF→IF transition in MsbA transporter using system-specific reaction coordinates α, β, and γ, describing protein global conformation.