Theoretical Studies Of Interactions Between Al-backbone Protein Ring Structure And Ring Sidechains Of Amino Acids

Aluminum is widely used in the antibacterial agent, food additives and cookingutensils as a kind of common metal. Research shows that aluminum elements candamage human brain cells, and it is a key factor leading to amyloid diseases, such asAlzheimer’s disease and Parkinson’s disease. Unfortunately, we still poorlyunderstand its potential therapeutic mechanism, which limits our ability to preventand cure the corresponding disease. Recently, Song and his coworkers found that thehydrated aluminum ion can form a stable ring structure on the peptide backbonethrough interacting with the amide nitrogen atom and the carbonyl oxygen atom byforming covalent bonds, which induced the irreversible damage to the protein andresulted in the inactivation of the protein. In our work, we have studied and simulatedthe interaction formation between the backbone ring structure Al-backbone and theamino acids (His, Phe, Trp and Tyr) with ring sidechains by the first principles ofQuantum Chemistry. It was observed that the Al-induced complex was able to stablybind to these sidechains in the absence of water molecules. Meanwhile, theAl-backbone ring can bind to the His sidechain but can not bind to the othersidechains in the presence of water molecules. The water-independent adsorption canbe attributed to the coordinate bond between the Al ion of the Al-induced backbonering structure and the N atom of His sidechain. However, Al-backbone ring structureinteracts with other amino acids through the cation-π and π-π interactions. We havecarried out a detailed analysis and studies of the new interaction formation. We haveproved the π-π interaction through the method of density difference, and furthervalidated the cation-π interaction by analyzing the distribution of positive andnegative charges. These findings are expected to provide a molecular understandingof the Al-related toxicity, and may be helpful in designing drugs for thoseaforementioned aluminum-linked diseases and encouraging treatment of Al-pollutedwater.