Characterizing the Conformational Dynamics of the Ribose Transporter B Protein in Escherichia coli: Enhanced Sampling...

We present a molecular dynamics simulation study of the E. coli ribose transporter protein B (RbsB), a conformationally labile protein found in the periplasm of the bacterium. The ribose transporter exhibits characteristics of both traditional type I and type II import systems. In our study, we observed the full conformational transition of the periplasmic binding protein RbsB for the first time. Our study revealed that in most scenarios (all but one) the conformational changes preceded the departure of ribose from the binding site, a process likely influenced by specific interactions at the binding interface. Indeed, our analyses of ribose binding revealed that specific salt bridges played a crucial role in stabilizing the closed conformation of RbsB. Our simulations also provided further evidence for a putative structural water molecule, which had also been observed from X-ray data. Crucially, our simulations were run with three different force fields: CHARMM36(m), AMBER ff19SB, and CHARMM36(m) with SIRAH coarse-grained water. This strategy enabled us to observe all of the conformational states that had been identified in structural studies. Thus, we argue that the subtle biases of individual force fields can be utilized to enhance conformational sampling.