TolC protein was found in many pathogenic Gram-negative bacteria. It is an outer membrane channel for expulsion of drug and toxin from the cell. In the causative agent for typhoid fever, Salmonella enterica ser. Typhi, the TolC outer membrane protein is also found to be antigenic. Since the lipid environment is an important modulator of membrane protein structure and function, therefore in order to study the membrane protein, TolC from Salmonella enterica serovar Typhi was assembled in two different lipid membranes, namely DMPE and POPE. The conformation of TolC from molecular dynamics simulation in DMPE and POPE bilayers was evaluated. S. Typhi TolC protein showed similar conformational dynamics to TolC proteins family. Flexibility of the protein is seen in the C-terminal, extracellular loops and α-helical region. Similar TolC conformation in both DMPE and POPE bilayers were observed which was the rotational motion of the C-terminal residues and extracellular loops. Nevertheless, hydrophobic matching effects of the TolC protein, particularly in the lipids lengthening and subtle movements of the β-barrel towards the lower leaflet in DMPE were exhibited. The study demonstrated the use of molecular dynamics simulation in revealing the differential effect on membrane protein and lipids on each other. In this case, POPE is more suitable lipids for further simulation of the S. Typhi TolC protein.