Download Biomolecules at interfaces at atomistic resolution

Project C1.1: Biomolecules at interfaces at atomic resolution
Project leader: Knecht (MPIKG)
Co-reviewer of Ph.D. thesis: Schoen (TUB)
US partner: Berkowitz (UNC)
Outline. The project is concerned with the interaction of biomolecules with lipid layers at an atomic
level. The method chosen here will be molecular dynamics (MD) computer simulation techniques.
Lipid monolayers at a water/vapor interface as models for bilayers will be used to mimic specific
experiments in the Brezesinski group from the Möhwald department. Three sample biomolecules
consisting of an antimicrobial or an amyloid peptide and DNA shall be investigated. The aim is to
understand or predict the conformational transition of the peptides upon adsorption to lipid
monolayers, the effect of the peptides on lipid
structure, and mechanisms of coupling DNA
to lipid layers. Detailed understanding of
these systems is of fundamental and medical
importance. Aiming at a quantitative understanding of these systems, biomolecules and
interfaces will be modelled in full atomic detail. The use of a full atomistic description is
Conformational polymorphism of an amphiphilic peptide (B18) computationally expensive which is one of the
in different environments from all-atom simulations in our lab. challenges of this project
The initial (left) and typical configurations in explicit water
(middle) or at a water/vapor interface (right) are shown.
Hydrophobic residues are depicted in yellow.
Research within the German group.
The
doctoral researcher will study biomolecules in
solution and at interfaces using MD simulations (J. Phys. Chem. B. 111, 4161 (2007)). By this
means, first, the 26-residue antimicrobial peptide NK-2 in solution or at an anionic lipid monolayer,
and an anionic monolayer in the absence of a peptide, will be simulated. Second, simulations of
the Alzheimer’s amyloid E (AE peptide in aqueous solution will be conducted. The helix-kink-helix
structure of NK-2 embedded in the parent protein and the partially helical structure of AE in a water/micelle system will be used as initial peptide configurations and methods to enhance sampling
of conformational space will be employed. Finally, the calcium-mediated coupling of DNA to a zwitterionic lipid monolayer will be studied by estimating the adhesion energy between DNA and the
monolayer in the presence and absence of calcium using thermodynamic integration.
Complementary work in US partner group. Cationic lipid monolayers in the absence and pres-
ence of AEwill be simulated in the Berkowitz group. The Berkowitz group has extensive experience in studies of lipid systems using MD simulation techniques and this project will complement
their current work on the interaction between zwitter- or anionic lipids and AE.
Status of the project. This project pertains to project area C1 in which biomolecules at interfaces
will be studied. The project shall be carried out in close collaboration with C1.2 (Rabe) in which
conformations of AEat cationic amphiphilic monolayers will be investigated using a scanning tunnelling microscope. The project is also related to B3.1 (Findenegg) devoted to the adsorption of
proteins to surface-functionalized nanopores and C2.3 (Hildebrandt) focused on the binding of proteins to lipid layers both using experimental techniques. In terms of methodology, there are links to
A1.1 (Stark), A2.1 (Schoen) and A3.1 (Schoen), B1.1 (Klapp) and C3.1 (Klapp), B2.1 (Weikl), and
C2.1 (Lipowsky), in which computational approaches will be used to study soft-matter nanostructures at interfaces on various length scales. This project will address the smallest (atomic) scale.
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