Classical molecular dynamic simulations and density functional theory are used to unveil the interaction of aluminum with various phosphorylated derivatives of the fragment KSPVPKSPVEEKG (NF13), a major multiphosphorylation domain of human neurofilament medium (NFM). Our calculations reveal the rich coordination chemistry of the resultant structures with a clear tendency of aluminum to form multidentate structures, acting as a bridging agent between different sidechains and altering the local secondary structure around the binding site. Our evaluation of binding energies allows us to determine that phosphorylation has an increase in the affinity of these peptides towards aluminum, although the interaction is not as strong as well-known chelators of aluminum in biological systems. Finally, the presence of hydroxides in the first solvation layer has a clear damping effect on the binding affinities. Our results help in elucidating the potential structures than can be formed between this exogenous neurotoxic metal and key sequences for the formation of neurofilament tangles, which are behind of some of the most important degenerative diseases.

经典的分子动力学模拟和密度泛函理论用于揭示铝与片段KSPVPKSPVEEKG（NF13）的磷酸化衍生物的相互作用，NFSP13是人类神经丝介质（NFM）的主要多磷酸化域。我们的计算揭示了所得结构的丰富配位化学，铝具有形成多齿结构的明显趋势，可充当不同侧链之间的桥联剂并改变结合位点附近的局部二级结构。我们对结合能的评估使我们能够确定磷酸化具有这些肽对铝的亲和力，尽管这种相互作用不如生物系统中众所周知的铝螯合剂那么强。最后，第一溶剂化层中氢氧化物的存在对结合亲和力具有明显的阻尼作用。我们的结果有助于阐明在这种外源性神经毒性金属和形成神经丝缠结的关键序列之间可能形成的潜在结构，而神经丝缠结是某些最重要的退化性疾病背后的原因。