Related Experiment Video
Updated: Jun 3, 2026
A Reproducible Intensive Care Unit-Oriented Endotoxin Model in Rats
Published on: February 20, 2021
Propofol Offers a Promising Therapeutic Strategy Against Sepsis via Inhibiting Rab5a-mediated Intracellular
Ghazi Elamin1,2, Pragasan Dean Gopalan1
1Department of Anaesthesiology & Critical Care, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
Introduction:
Propofol has reported to have anti-inflammatory effects and has been suggested to reduce TLR4 membrane expression via Rab5a. We aimed to characterize, at atomic resolution, propofol's binding mode to Rab5a and its effect on Rab5a dynamics using in-silico methods.
Methods:
We performed molecular docking, 300-ns molecular dynamics (MD) simulations of apo-Rab5a and Rab5a-propofol complex, MM/GBSA binding free energy calculations, perresidue energy decomposition, RMSD/RMSF/RoG/SASA analyses, and principal component analysis (PCA).
Results:
We show that propofol adopts a stable binding pose, with an MM/GBSA ΔG!"#$, -21.72 kcal/mol, and that propofol binding reduces Rab5a flexibility, increases compactness, and shifts principal component motions toward correlated, lower-amplitude dynamics. Key interacting residues include Glu36, Ala42, and Asp61.
Discussion:
The results provide atomistic evidence supporting the hypothesis that propofol stabilizes Rab5a in a conformational state that may limit TLR4 trafficking to the plasma membrane. These findings align with prior cellular observations and generate residue-specific hypotheses testable experimentally. Study limitations include reliance on computational methods, a single ligand-binding mode, and the absence of entropy contributions. Experimental validation is required to confirm physiological relevance.
Conclusion:
Our in-silico results provide mechanistic hypotheses (binding site, residue hotspots, and dynamic stabilization) that are consistent with previous cellular work and warrant biochemical validation.
