title: Molecular dynamics simulations on networks of heparin and collagen.
abstract: Synthetic scaffolds containing collagen (Type I) are of increasing interest for bone tissue engineering, especially for highly porous biomaterials in combination with glycosaminoglycans. In experiments the integration of heparin during the fibrillogenesis resulted in different types of collagen fibrils, but models for this aggregation on a molecular scale were only tentative. We conducted molecular dynamic simulations investigating the binding of heparin to collagen and the influence of the telopeptides during collagen aggregation. This aims at explaining experimental findings on a molecular level. Novel structures for N- and C-telopeptides were developed with the TIGER2 replica exchange algorithm and dihedral principle component analysis. We present an extended statistical analysis of the mainly electrostatic interaction between heparin and collagen and identify several binding sites. Finally, we propose a molecular mechanism for the influence of glycosaminoglycans on the morphology of collagen fibrils. Proteins 2017; 85:1119-1130. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Institut für Biochemie, Ernst-Moritz-Arndt-Universität Greifswald, Felix-Hausdorff-Straße 4, Greifswald, 17487, Germany.
authors.forename: Martin
authors.identifier: 0000-0002-2689-2428
authors.initials: M
authors.lastname: Kulke
authors.affiliation: Institut für Biochemie, Ernst-Moritz-Arndt-Universität Greifswald, Felix-Hausdorff-Straße 4, Greifswald, 17487, Germany.
authors.forename: Norman
authors.initials: N
authors.lastname: Geist
authors.affiliation: Institut für Biochemie, Ernst-Moritz-Arndt-Universität Greifswald, Felix-Hausdorff-Straße 4, Greifswald, 17487, Germany.
authors.forename: Wenke
authors.initials: W
authors.lastname: Friedrichs
authors.affiliation: Institut für Biochemie, Ernst-Moritz-Arndt-Universität Greifswald, Felix-Hausdorff-Straße 4, Greifswald, 17487, Germany.
authors.forename: Walter
authors.initials: W
authors.lastname: Langel
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D001665:Binding Sites; D001842:Bone and Bones / Q000737:chemistry; D003094:Collagen / Q000737:chemistry*; D024042:Collagen Type I / Q000737:chemistry*; D006025:Glycosaminoglycans / Q000737:chemistry*; D006493:Heparin / Q000737:chemistry*; D006801:Humans; D056004:Molecular Dynamics Simulation; D054802:Molecular Imprinting; D010455:Peptides / Q000737:chemistry*; D025341:Principal Component Analysis; D011485:Protein Binding; D000072756:Protein Conformation, alpha-Helical; D000072757:Protein Conformation, beta-Strand; D054730:Protein Interaction Domains and Motifs; D055672:Static Electricity; D013816:Thermodynamics; D023822:Tissue Engineering; D054457:Tissue Scaffolds
chemical_list: D024042:Collagen Type I; D006025:Glycosaminoglycans; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D006493:Heparin; D003094:Collagen
keywords: fibril overlap region; principle component analysis; protein interaction; protein structure; replica exchange; telopeptides