# Characterizing the Conformational Dynamics of the Ribose Transporter B Protein in Escherichia coli: Enhanced Sampling via Multiple Force Fields

## TL;DR

This study uses molecular dynamics simulations to explore how the ribose transporter protein RbsB in E. coli changes shape, revealing new insights into its conformational dynamics and binding mechanisms.

## Contribution

The study is the first to observe the full conformational transition of RbsB and demonstrates how using multiple force fields can enhance conformational sampling.

## Key findings

- Conformational changes in RbsB typically precede ribose release from the binding site.
- Salt bridges at the binding interface play a key role in stabilizing the closed conformation of RbsB.
- A putative structural water molecule was confirmed through simulations and X-ray data.

## Abstract

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.