The Impact Of Hydrophobic And Charged Surface On The Aggregation Structures Of Polypeptides: A Molecular Dynamics Simulation Study

Peptide fibrils have been one of the most promising biomaterials due to their exceptional mechanical properties, which are comparable to that of spider silks. It is known that more than half of all proteins and peptides can interact with various membranes and surfaces. After adsorption on the surfaces, they form amorphous aggregates or ordered β-sheet structures through intermolecular attraction. On the other hand, the existing amorphous aggregates formed in solutions transform into ordered structures by conformational changes on the surfaces. In this paper, we investigated the impact of hydrophobic surface on the transformation of amorphous aggregates by polyalanines(contains 12 alaines, A12) into ordered β-sheet structures, as well as the self-assembly process and mechanism of short polypeptides(Ace-KLVFFAE-NH2) on negatively charged surface by molecular dynamics(MD) simulations. The major research contents and conclusions are as follows:1. We systematically studied the conformational changes and structural adjustment/rearrangement of amorphous aggregates formed by polyalanines(A12) in water and on the hydrophobic surface at different temperatures, respectively. The hydrophobic surface was composed of self-assembled alkanethiol monolayer terminated with methyl(-CH3) group. Our simulation results showed that amorphous aggregates tend to maintain spherical conformations to keep the original minimum hydrophobic area in water, and that the transformation into β-sheet structures is via “from inside out” mode when temperature is higher than 300K(the β-sheet growth can be neglected below 300K). Moreover, the β-sheet growth fits a negative exponential growth model, ?(t)=A0-A1exp(-t/t1). By contrast, the transformation from amorphous aggregate into β-sheet structures is via “from bottom up, then from outside in” mode. The β-sheet growth on the hydrophobic surface fits a similar negative exponential model, but with bigger A0, which suggests that the β-sheet growth on the hydrophobic surface is faster than that in water. This is due to the fact that the hydrophobic surface not only enhances local peptide concentration, but also reduces the conformational entropy of polypeptide. In addition, it was found that the β-sheet growth rate on the hydrophobic surface is highest at 340 K.2. We investigated the temperature-dependent self-assembly behavior of short peptide(Ace-KLVFFAE-NH2) in water and on negative charged surface by molecular dynamics simulations, respectively. The negatively charged surface was composed of self-assembled alkanethiol monolayer terminated with carboxyl(-COO) group. Our simulation results showed that peptides in water self-assembly into spherical amorphous aggregates, while they adsorb on the negatively charged surface in an “inverse U” shape through the electrostatic attractions between lysine and the negatively charged surface, as well as between glutamic acid and cation(Na+) on the surface, to ultimately form different-sized amorphous aggregates. Higher temperature accelerates β-structure growth by enhancing mean square displacement of peptides.