Salmonella typhimurium is a Gram-negative bacterium responsible for human diseases including gastroenteritis and typhoid fever and its quorum sensing system is currently being intensively researched. Molecular modeling and binding site analysis of SdiA homolog, a putative quorum sensor of the LuxR family and responsible for S. typhimurium pathogenecity revealed a high structural homology of their active site with three other LuxR family proteins LasR from Pseudomonas aeruginosa, TraR from Agrobacterium tumifaciens and CviR from Chromobacterium violaceum. The results show that all the LuxR family proteins harbor three conserved amino acids Tryptophan (W67) and Aspartic acid (D80) for formation of hydrogen bridges and Tyrosine (Y71) for the hydrophobic interactions (corresponding to their position in S. typhimurium SdiA) with acyl homoserine lactones (AHL) -dependent transcriptional regulators. However, in addition to the above conserved residues, Arginine (R60) also plays an important role in S. typhimurium SdiA binding with its AHL auto inducers and the complex is found to be stronger because of the interactions between nitrogen atoms of Arginine with the carbonyl oxygen in the lactone ring of AHL. The specific binding patterns would be helpful in guiding both enzymatic studies as well as design of specific inhibitors to overcome S. typhimurium pathogenecity.