Molecular Dynamic Study Of Self-Assembly Of Polyalanines With Different Lengths On Hydrophobic Surface

Many normal soluble proteins and peptides may aggregate pathologically into insolubleamyloid fibrils that are mainly composed of β-sheets. Accumulation of the amyloid fibrils onor among neurons results in many fatal neurodegenerative diseases, such as Alzheimer’s,Parkinson’s, and prion diseases. On the other hand, the amyloid fibers possess exceptionalmechanical properties that are comparable to spider silks. Thus, understanding theself-assembly mechanisms of proteins and peptides is important not only for the effective curefor neurodegenerative diseases, but also for developing new biological materials and devices.In the present work, we studied the self-assembly mechanisms of polyalanines with differentchain lengths in water and on the hydrophobic surface by molecular dynamics simulationtechnique. The hydrophobic surface was composed of self-assembled alkanethiol monolayerterminated with methyl （–CH₃） group. Our simulation results show that the growth rate ofβ-structures decays exponentially in water; while on the hydrophobic surface polyalaninesform β-structures rapidly. The formation process of β-structures on the hydrophobic surface iscomposed of two stages, and each of them fits linear growth model. Furthermore, we studiedthe effects of the hydrophobic surface on the conformations of polyalanines. It was found thatthe polyalanines prefer to assume stretched conformations with orientation-ordered sidechains on the hydrophobic surface. This suggests that the hydrophobic surface greatly reducesthe conformational entropy of polyalanines, which favors the β-structure formation.Meanwhile, the polyalanines adsorbed on the hydrophobic surface quickly, leading to theincrease of local peptide concentration and further acceleration of β-structure formation.Therefore, the accelerated β-structures growth on the hydrophobic surface results from theincrease of local peptide concentration and the decrease of conformational entropy ofpolyalanines. In addition, the growth rate of β-structures is dependent on the chain length. Itwas found that the β-structures growth rate increases with increasing chain length in the earlystage of aggregation process, while it decreases as the chain length increases in the middleand late stages. Our simulation results provide insights on understanding the self-assembly ofpolypeptides on the hydrophobic surface and developing new materials.