School of Analytical Sciences Adlershof

Revealing secrets of material specific peptide adhesion: From advanced NMR analysis to computational process modeling

Co-supervisor 1: Hans G. Börner (HU-Berlin)
Co-supervisor 2: Marcus Weber (Zuse Institute Berlin, ZIB)
Collaborator(s): Erhard Kemnitz (HU), Janina Kneipp (HU)
Complex of topics: B3 Analysis tools for dynamic interfaces to understand nanostructures

The adhesive system of marine mussels stimulated intensive interdisciplinary research.[Science 1981, Annu. Rev. Mater. Res. 2011] Mussels adhere onto virtually any hard substrate in hostile environments and outperform technical wet-glues. Besides these universal and complex protein based adhesives, 12mer peptides can be selected by biocombinatorial means to exhibit highly specific adhesion onto material surfaces.[Nature 2000] Those material specific adhesives promise a scope of next generation applications from nanoengineering of nanoparticle surfaces, to specific glues for nerve surgery.[ACS Macro Lett. 2012; J. Am. Chem. Soc. 2012]
The effects on the molecular scale, which originate the material specific adhesion of peptides are, however, by far not understood. Soft multipoint interactions, surface related docking, locking of peptide conformations and surface induced folding processes are discussed.[JACS 2011]
Objectives of the present project are the development of analytical tools and their companion with computational methods to gain insight into material specific adhesion. Advanced NMR analytics such as solution-based nuclear Overhauser and saturation transfer difference (STD) spectroscopies under transient binding conditions as well as surface enhanced local Raman spectroscopy (SERS) probing will be combined with modern molecular simulation to investigate dynamic interactions of peptides with material surfaces and thus elucidating mechanisms of recognition.
Focus will be set on the understanding of three recently selected peptides, showing specific adhesion onto surfaces of (i.) gold, (ii.) aircraft aluminum and (iii.) magnesium fluoride. The adhesive processes will be analyzed by advanced NMR techniques revealing insight into peptide surface contacts and contact developments throughout the adhesion process. The results will be accompanied with SERS-probing to analyze changes of vibrational dynamics of the surface adhered peptides. Based on those analytical data, molecular modeling of peptide conformation on the surface and conformational pathways during peptide adhesion process will be performed and reveal the origin of material specific adhesion on the molecular level. The discussed opinions about specific peptide adhesion should be modeled and validated. With the aid of atom-based models of surfaces and peptides (parametrization inside the software package GROMACS) and by using a sophisticated statistical thermodynamics software platform ZIBMolPy with domain decomposition and free-energy estimation [SIAM JMMS 2007, Lecture Notes 2013], adhesion scenarios can be analyzed thermodynamically. Moreover, kinetic effects have to be simulated and recent non-thermodynamic effects such as "rebinding effects" [JCP 2012] will be taken into account requiring new computational method developments.

2nd SALSA doctoral project call (Download PDF)