Molekulare Modellierung der Bindung von Peptiden und Proteinen an Oxidkeramikoberflächen

• Applicant: Professor Dr. Jürgen Pleiss
• Subject Area: Synthesis and Properties of Functional Materials ; Materials in Sintering Processes and Generative Manufacturing Processes ; Mechanical Properties of Metallic Materials and their Microstructural Origins
• Term: from 2009 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 112803434

• Final Report Year: 2014

Final Report Abstract

Adsorption of 6- and 12-mer peptides derived from phage display libraries on the polar ZnO(0001)-O terminated surface and the nonpolar ZnO(1010) surface was studied using molecular dynamics simulations. The calculated free energy of adsorption was in agreement with their experimentally determined relative binding strength. All peptides bind better to the polar than to the nonpolar surface. The binding strength is dominated by electrostatic interactions: strong binders have a high positive charge, while weak binders have low positive or even negative charge. However, sequence, structure, and dynamics of the peptide also contribute to the binding strength. A strong binder is characterized by three properties: (1) a number of 3-4 positively charged residues; (2) histidine near the N-terminus, glycine or proline in the center, arginine or lysine near the C-terminus; and (3) high flexibility in water, especially no secondary structure formation. The modeling study also highlighted the important role of interfacial water molecules for the adsorption of the peptide on the ZnO surfaces. Three constructs were investigated: 12-mer peptides derived from phage display, synthetic fluoresceinlabeled 12- and 6-mer peptides, and a fusion protein consisting of TrxA, 25 copies of the good binder zno1, and GFP. A fluorometric assay was established to experimentally quantify the adsorption of synthetic fluorescein-labeled peptides and the fluorescent fusion protein on ZnO particles.

Publications

• (2012) Bioinspired mineralization of zinc oxide in presence of ZnO-binding peptides. Biointerface Res Appl Chem 2: 380-391
  Baier J, Naumburg T, Blumenstein NJ, Jeurgens LPJ, Welzel U, Do TA, Pleiss J, Bill J
  
• Peptide–zinc oxide interaction: Finite element simulation using cohesive zone models based on molecular dynamics simulation. Computational Materials Science, Volume 95, December 2014, Pages 320-327
  Schäfer I, Lasko G, Do TA, Pleiss J, Weber U, Schmauder S