title: Conformational exploration of two peptides and their hybrid polymer conjugates: potentialities as self-aggregating materials.
abstract: In this work we elucidate the conformational preferences of two amyloid-forming peptides, Arginine-Vasopressin and Neuromedin-K, and two new biomacromolecular conjugates obtained by linking the two peptides to a polyester (poly(R-lactic acid)) chain. The conformational properties of the new hybrid conjugates have been assessed through molecular dynamics simulations and compared to those of their individual components. Our results suggest that the free unconjugated peptides tend to adopt backbone arrangements which resemble a β-hairpin shape, a conformation which has been reported to facilitate amyloid self-aggregation. The backbone conformational preferences of the unlinked peptides are maintained in the peptide-polymer hybrid. Yet significant differences in the side-chains nonbonding interactions patterns were detected between the two states. This suggests that the conformational profile of the peptides' backbones is preserved when linked to the polymer, maintaining the amyloid precursor-like structure. Additionally, several hydrodynamic parameters were computed for both the polylactic acid and for the conjugates: no significant differences were observed, which suggests that the peptide moiety of the hybrid does not significantly affect the conformational tendencies of the polymer chain. Combined, our results provide a conformational exploration of two amyloid-forming peptides and first steps toward the design of two feasible self-aggregating hybrid materials.
authors.affiliation: Department of Compuer Science, University of Massachusetts, Boston, 02125, United States. nurit.haspel@umb.edu
authors.forename: Nurit
authors.initials: N
authors.lastname: Haspel
authors.forename: Adèle D
authors.initials: AD
authors.lastname: Laurent
authors.forename: David
authors.initials: D
authors.lastname: Zanuy
authors.forename: Ruth
authors.initials: R
authors.lastname: Nussinov
authors.forename: Carlos
authors.initials: C
authors.lastname: Alemán
authors.forename: Jordi
authors.initials: J
authors.lastname: Puiggalí
authors.forename: Guillem
authors.initials: G
authors.lastname: Revilla-López
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry*; D001127:Arginine Vasopressin / Q000737:chemistry*; D019344:Lactic Acid / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D015287:Neurokinin B / Q000737:chemistry*; D011091:Polyesters; D011108:Polymers / Q000737:chemistry*; D017433:Protein Structure, Secondary
chemical_list: D000682:Amyloid; D011091:Polyesters; D011108:Polymers; D001127:Arginine Vasopressin; D019344:Lactic Acid; C033616:poly(lactide); D015287:Neurokinin B