The ProX protein in Escherichia coli binds to glycine betaine, facilitating the resistance of cells to environmental osmotic stress.To understand the osmotic regulation mechanism in Escherichia coli and to develop new natural bacterial osmoregulation agents, this study aimed to identify potential ligands that could bind to the ProX domain.The study employed high-throughput virtual screening and molecular docking techniques to screen for potential ligand compounds within the MedChemExpress natural compound library, followed by credibility verification using molecular mechanics-generalized Born surface area calculations and 100 ns of molecular dynamics simulations.Results showed that d-fagomine strongly interacted with key residues at the ProX active sites (such as GLY141, GLU20, ILE17, TRP140, TRP188, and TYR186), through hydrogen bonds and hydrophobic interactions.Furthermore, the flexible docking score (-12.266 kcal/mol) and Gibbs binding free energy (-40.05 kcal/mol) of the d-fagomine-ProX complex were better than those of the glycine betaine-ProX complex (-12.194 kcal/mol and -35.31 kcal/mol).These findings indicated that the d-fagomine-ProX complex could exhibit exceptional stability with promising potential as a new osmoregulation agent.This research provides new perspectives and methods for the design and development of innovative osmoregulation inhibitors or compatible solutes.
XU Wenjing
,
SUN Rong
,
ZHOU Xianxuan
. Discovery of novel ProX ligands through virtual screening and molecular dynamics simulation[J]. Food and Fermentation Industries, 2025
, 51(8)
: 8
-12
.
DOI: 10.13995/j.cnki.11-1802/ts.039550
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