Aluminium is widely used as an antimicrobial coagulant,food additive,and cookware.However,many reports indicate that aluminium may be a critical factor in many amyloid diseases,such as Alzheimer’s disease and Parkinson’s disease.Unfortunately,the underlying mechanism is still poorly understood,which limits efforts to prevent and treat these diseases.In this paper,using an ab initio method,we studied the interaction of Al-backbone ring structure with theπ-electron-rich sidechains of His,Phe,Trp,and Tyr.We found that in the absence of water,the Al-backbone ring can stably bind with those sidechains.In the presence of water,the Al-backbone ring can bind to the His sidechain and cannot bind to the other sidechains.As revealed by further investigations,this could be attributed to the fact that there was a coordinate bond of the Al-backbone ring with the His sidechain,while there were theπ-πstacking and cation-π-like interactions with the other sidechains.These findings potentially provide a molecular understanding of Al-related toxicity,and may be helpful in designing drugs for those aforementioned aluminum-linked diseases and encourage treatment of Al-polluted water. Aluminum is widely used as an antimicrobial coagulant, food additive, and cookware. Host, many reports indicate that aluminum may be a critical factor in many amyloid diseases, such as Alzheimer’s disease and Parkinson’s disease. Unfortunately, the underlying mechanism is still poorly understood, which limits efforts to prevent and treat these diseases. In this paper, using an ab initio method, we studied the interaction of Al-backbone ring structure with theπ-electron-rich sidechains of His, Phe, Trp, and Tyr. We found that in the absence of water, the Al-backbone ring can stably bind with those sidechains. In the presence of water, the Al-backbone ring bind to the His side chain and can not bind to the other side chains. As revealed by further investigations, this could be attributed to the fact that there was a coordinate bond of the Al-backbone ring with the His side chain, while there were the π-π stacking and cation-π-like interactions with the other side chains. the findings potentially p rovide a molecular understanding of Al-related toxicity, and may be useful in designing drugs for those who aluminum-linked diseases and encourage treatment of Al-polluted water.