title: The self-assembly mechanism of fibril-forming silk-based block copolymers.
abstract: Triblock copolymers consisting of a silk-based ((Gly-Ala)(3)Gly-Glu) repeat flanked by hydrophilic outer blocks self-assemble into micrometer long fibrils in response to a trigger. Since the exact mechanism of the fibril formation remains unclear, we employ a multiscale modelling approach in combination with rare event simulations to elucidate key processes. Atomistic scale simulations on the silk-based block suggest a mechanism in which a polypeptide prefolded into a β-roll structure docks to the growing end of a fibril through the formation of Glu-Glu sidechain contacts. Subsequently it can slide to the optimal position before water is expelled to form a dry interface between the fibril end and the attaching block copolymer. In addition, we find that the folded state of the silk-based block is further stabilised through interactions with its neighboring block. Templated folding may also play a role in case a partially folded polypeptide attaches. The coarse-grained simulations indicate that the attachment and subsequent sliding is mediated by the hydrophilic flanks in a size dependent manner. The hydrophilic blocks prevent random aggregation and allow growth only at the end of the fibril. Our multiscale approach may be used for other fibril-forming peptides.
authors.affiliation: Van 't Hoff Institute for Molecular Sciences, Universiteit van Amsterdam, Science Park 904, 1098 XH, Amsterdam, The Netherlands.
authors.forename: Marieke
authors.initials: M
authors.lastname: Schor
authors.forename: Peter G
authors.initials: PG
authors.lastname: Bolhuis
mesh_terms: D004151:Dipeptides / Q000737:chemistry; D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D011108:Polymers / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D047011:Silk / Q000737:chemistry*
chemical_list: D004151:Dipeptides; D011108:Polymers; D047011:Silk; C094686:glutamyl-glutamic acid