Length-dependent β-sheet growth mechanisms of polyalanine peptides in water and on hydrophobic surfaces

Abstract

Fibrillar assemblies by peptides are becoming one of the most promising nanomaterials due to their exceptional properties. The self-assembly of peptides into β sheets is a critical step in the fibrillization pathway. We investigated the length-dependent β-sheet growth mechanisms of polyalanine [poly(A)] peptides consisting of 6 to 24 alanines (A6 to A24) in water and on the hydrophobic surface, respectively, by molecular dynamics simulations. β-sheet growth behavior in water fits negative exponential growth model, showing that β-sheet growth rate decays exponentially with time. Meanwhile, increasing chain length leads to an accelerated decay of the β-sheet growth rate. By contrast, β-sheet growth on the surface from A6 to A18 occurs in two consecutive stages, both of which fit linear growth models. β-sheet growth rate in the first stage increases as chain length is increased, while the intermediate length peptide A12 has the highest β-sheet growth rate in the second stage. β-sheet growth behavior of A24 on the surface still fits negative exponential model. Overall, the hydrophobic surface accelerates β-sheet growth by enhancing local concentration and reducing conformational entropy of poly(A) peptide, and the β-sheet growth of the intermediate length peptide A12 is the fastest on the surface. Our simulation results shed light on understanding the accelerated peptide fibrillization on the hydrophobic surface.

Silk Fibroin–Substrate Interactions at Heterogeneous Nanocomposite Interfaces

“…MD simulations are ideally suited for modeling intertwined processes and can probe detailed chemical and physical interactions occurring between biopolymers and surfaces . However, most simulations have focused on adsorption of short peptides onto hydrophobic surfaces . For example, MD simulations were used to investigate the adsorption and aggregation of short peptides (GA) 4 and (GV) 4 on a rough hydrophobic surface, where peptides aggregated into layered β‐sheet structures .…”

“…For example, MD simulations were used to investigate the adsorption and aggregation of short peptides (GA) 4 and (GV) 4 on a rough hydrophobic surface, where peptides aggregated into layered β‐sheet structures . Most recently, a study investigated adsorption of ten polyalanine peptides with up to 24 repeats onto a hydrophobic surface . These results indicated that a hydrophobic surface can accelerate β‐sheet growth by enhancing local concentration and reducing conformational entropy of a peptide sequence.…”

Marine Structural Protein Stability Induced by Hofmeister Salt Annealing and Enzymatic Cross-Linking

“…13,20−22 The Ala-, His-rich segment exhibits the strongest peptide−peptide interactions, which are pH dependent with intermolecular bonding promoting β-sheets. 23 For suckerin, His provides supplemental pH-dependent support. At low pHs, His can increase protein solubility and, when near neutral pH, His can deprotonate, imparting more aromatic character on its imidazole which can then facilitate π−π stacking.…”

“…Suckerin is a globular protein with alanine- (Ala, A), threonine- (Thr, T), and His-rich nanoconfined β-sheets in a Gly-, leucine- (Leu, L), and tyrosine- (Tyr, Y) rich amorphous phase (Figure ). ,− The Ala-, His-rich segment exhibits the strongest peptide–peptide interactions, which are pH dependent with intermolecular bonding promoting β-sheets . For suckerin, His provides supplemental pH-dependent support.…”

Characterizing the Switching Transitions of an Adsorbed Peptide by Mapping the Potential Energy Surface

“…For example, it is implicated in the fouling and degradation of medical implants, 16 and may play a role in the fibrillation of proteins associated with degenerative brain diseases such as Alzhemier's. [17][18] Given the widespread applications of peptide and protein adsorption, it is desirable to understand the molecular processes involved in this phenomenon. All-atom molecular dynamics has been widely used to study preferred structures of adsorbed peptides, [19][20] and studies in recent years have succeeded in estimating the free energy of adsorption, [21][22][23] and proposing mechanisms for the peptide adsorption process.…”