Alpha Helix Peptides On The Surface Of The Graphite Layer Adsorption And Conformation Change And Polymerization Of Two Atoms Of Molecular Dynamics Simulation

Protein-surface interaction is a common and complex phenomenon of nature. It has draw significant attention due to its important rold in many fields, such as protein conformational transition and design of biomaterials. Surface may perturb or stabilize the native structure of proteins. Clinical disorder including Alzheimer’s disease, prion disease, and type II diabetes are considered to be associated with protein conformational transition from a-helix/random-coil toβ-sheet. It is of fundamental importance to understand the conformational conversion triggering the amyloidogenesis.Recent circular dichroism spectroscopy and scanning tunneling microscopy study reported that a de novo designedα-helical peptide (with amino acid sequence DELERRIRELEARIK) would transform toβ-sheet structure as well as random coil structure upon the addition of graphite particles to the peptide solution and aggregate into orderedβ-sheet-rich assemblies at graphite surface. However, the atomic-level information about the dynamics of early-stage conformational transition at water-graphite interface and the driving force underlying the structural transition are largely unknown. In this study, we have investigated the conformational dynamics of two chains of theα-helical peptide in the absence and presence of a graphene sheet by performing all-atom molecular dynamic (MD) simulations in explicit solvent. Our simulations show that, consistent with the signal measured experimentally under physiological buffer conditions, two chains are mostly dimeric and keep a-helical structure in solution, while they unfold and assemble into an amorphous dimer at graphene surface. Theβ-sheet conformation is not observed in all MD runs within the 15-200 ns timescale, which indicates that theα-helix toβ-sheet transition for this short peptide at graphite surface is a slow process, similar to the slow transition dynamics of globular protein reported experimentally.By analyzing all the MD trajectories, we found that 1) the formation ofα-helical dimer in solution is mostly driven and stabilized by inter-peptide hydrophobic interactions; 2) the adsorption and theα-helix unfolding of the peptide at graphene surface is initiated from the C-terminal region due to strong interactions between residues Argl3-Ile14-Lysl5 and graphene surface; 3) the extent of helix unfolding strongly depends on the interaction strength between the peptide and graphene surface; 4) the dimerization of two unfolded peptide chains at graphene surface results from the interplay between peptide-graphene and peptide-peptide interactions. This study would provide significant insight into the detailed mechanism of graphite-induced conformational transition and dimerization prior to the formation ofβ-sheet assemblies of this short syntheticα-helical peptide.