Prokaryotes and Eukaryotes such as bacteria, plants, animals etc., uptake essential nutrients through transporters. Transporters are carrier proteins that transport the molecules in and out of the cell. These proteins undergo large conformational changes such as inward facing (open to the cell), occluded (closed at both ends) and outward facing state (close to the cell) to transport the molecules. Unlikely, it’s not possible to obtain crystal structures of different states using experimental procedures as this class of proteins are highly flexible in nature. Using Blue Waters, we performed hundreds of microsecond-long simulations of membrane transporter proteins to predict the key conformational states to understand the substrate transport mechanism. We identified crucial residues that acts as a barrier for conformational switching of transporter form one state to other. For the first time, we characterize the complete cycle of transporter proteins using unbiased simulation using the Blue Waters supercomputer.

Balaji Selvam, Shriyaa Mittal and Diwakar Shukla. Understanding the conformational switches in membrane transporter proteins using Blue Waters. Blue Waters Symposium, May 16-19, 2017, Oregon.