Aromatic stacked salt bridges are increasingly observed to play an important role in biology, suggesting that the two separate weak interactions cooperate with each other to mediate molecular recognition in a biological solution. In this thesis an in depth study was carried out in attempt to find the contribution of the guanidinium-carboxylate-aromatic triad in biological systems. Two different small molecule systems are used to carry out the study. From the results of the two chapters I proposed here that stacking aromatic ring enhances the salt bridge through desolvation effect. This hypothesis was also tested in a protein-protein interaction (Grb2 SH3 domain/SOS interaction). The most ideal peptide inhibitor cannot be obtained due to the synthetic difficulties. Limited result showed that increasing the hydrophobic area of the hot spot in this protein-protein interaction enhances the interaction. In researching the guanidinium-carboxylate-aromatic triad, we were inspired to study the pre-organization effect of 1,3,5-triethyl-2,4,6-trisubstituted benzene template. A computational and literature study done in this thesis showed that the installation of ethyl or methyl groups at 1,3,5 positions leads to consistent increases in binding affinity relative to unsubstituted hosts, but the amount of increase is non-trivial and varies with different substitutes. The installation of ethyl or methyl groups at 1,3,5 positions leads to consistent but relatively small increases in binding affinity relative to unsubstituted hosts. / Graduate