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Volume 10, Issue 8 (Suppl)

J Proteomics Bioinform, an open access journal

ISSN: 0974-276X

Structural Biology 2017

September 18-20, 2017

International Conference on

Structural Biology

September 18-20, 2017 Zurich, Switzerland

Matthias Buck, J Proteomics Bioinform 2017, 10:8(Suppl)

DOI: 10.4172/0974-276X-C1-0100

Solution NMR relaxation and µs molecular dynamics simulations of dynamic protein-protein and

protein-membrane complexes

Matthias Buck

Case Western Reserve University, USA

t is now recognized that protein-protein interactions in solution are often dynamic, especially if the binding affinities are only

moderately strong. Dynamics originate in part from the interconversion between structures of the protein complex, e.g. one

bound state that is in equilibrium with one or several alternate configurations. We determined the structure of such a complex

using NMR restraints and saw the transitions between different configurations in microsecond length all-atom molecular

dynamics simulations. Recently, we also studied the dissociation process of mutant complexes which had a weakened primary

interaction interface. Those simulations suggested that there is no single dissociation pathway, but that the separation first

involves transitions to binding interfaces with fewer/weaker contacts. Comparison is made between experimental NMR

relaxation measurements on the ps-ns as well as µs-ms timescale with the microsecond all atom simulations, also in the

context of new simulations of the protein association process. The functional significance of the protein complex alternate

states and their dynamics are discussed. In a second part of the presentation, we consider a second system involving transient

interactions; this time between K-Ras and the lipid bilayer of the plasma membrane. Our recent simulations the full length

GTPase at different membranes reveal the underlying rules of the interactions, emphasizing electrostatic contacts but also

protein topology. Again, simulations are compared with NMR experiments, carried out at model systems for the membrane.

Biography

Matthias Buck has completed his BA, MA from the University of Cambridge and pursued his DPhil from the University of Oxford. He was a Group Leader since

2002 and Professor since 2014. The Buck laboratory studies two receptor families responsible for cell guidance and positional maintenance (Plexins and Ephrins),

both with key involvement in cardiovascular and neuronal development and disease, esp. cancer. They use a wide range of structural biology (solution NMR / x-ray

crystallography) and protein biophysical tools (CD, fluorescence spectroscopy, ITC and SPR) in a problem oriented approach. Part of the laboratory also pursues

computational modeling and molecular dynamics to provide additional perspective on the problems, provide new insights into the experimental data and to suggest

further studies. Small GTPases and their interaction with the plexin receptor cytoplasmic domains has been a major focus of the laboratory and recently they have

become very interested in protein-membrane interactions; both the transmembrane regions of the receptors as well as the transient interactions of receptor and

GTPase domains with membranes.

Matthias.Buck@case.edu

Figure1:

K-Ras4A in two preferred orientations at

a membrane containing anionic lipids.