Biomolecular Self-Assembly

Founded in 08/2015, the group is focused on biologically relevant molecules and macromolecular complexes, where intermoleculer interactions play a pivotal role in manifesting biological function. We are particularly interested in molecular level understanding of structure, function and mechanisms of membrane active compounds. Our aim is to study and design natural and nature-mimicking species which can be further developed in biomedical applications targeting organism-specific membranes.

Group leader: 
Research interests: 

Membrane Active Biomolecules

We focus on both natural and non-natural membrane active peptides and their interactions with specific lipid components that can be found in biologically relevant target membranes. We aim to design artificial peptidic foldamers that can undergo favorable conformational changes upon interaction with specific lipid components. We study these interactions with theoretical (QM&MD) and experimental methods in model membranes. We apply both 2D and 3D membrane models (supported lipid bilayers and liposomal systems), and investigate their structures and interactions using sum-frequency generation vibrational spectroscopy (SFG) and polarized light spectroscopy (CD, LD).

Related References

  1. T. Keszthelyi, K. Hill, É Kiss Interaction of Phospholipid Langmuir Monolayers with an Antibiotic Peptide Conjugate J. Phys. Chem. B, 2013, 117 (23), pp 6969–6979
  2. J. Johansson, E. Hermansson, N. Kann, B. Nordén, T. Beke-Somfai: d-Peptides from RuAAC-Derived 1,5-Disubstituted Triazole Units, Eur. J. Org. Chem. 2014, 13, 2703-2713
  3. N. Kann, J. R. Johansson, T. Beke-Somfai*: Conformational properties of 1,4- and 1,5-substituted 1,2,3-triazole amino acids – building units for peptidic foldamers, Organic & Biomolecular Chemistry, 2015, DOI: 10.1039/C4OB02359E
  4. T. Beke, A. Czajlik, B. Bálint, A. Perczel: A Theoretical Comparison of Self-Assembling a- and b-Peptide Nanostructures: Toward Design of b-Barrel Frameworks ACS Nano, 2008, 2, 545-553
  5. T. Beke, I. G. Csizmadia, A. Perczel: Theoretical study on tertiary structural elements of b-peptides: Nanotubes formed from parallel-sheet-derived assemblies of b-peptides J. Am. Chem. Soc., 2006, 128, 5158-5167

Complex Biomolecular Machines

In a wide range of biological activities, from cell locomotion to membrane transport, Nature deploys numerous sophisticated molecular machines which have become highly optimized for performance and controllability. Rational design and engineering of similarly complex biosystems is a very exciting field with a potential to dramatically alter future’s medicine or industrial biochemistry. However, to overcome major challenges in design of artificial enzymes, the precise understanding of control mechanism on key reaction steps by larger molecular scale structure and dynamics is required. FoF1 ATP synthase is interesting as a model system: a delicate molecular machine synthesizing or hydrolyzing ATP utilizing a rotary motor. (1-2) ATP synthase is a member of the RecA-like helicase family, and it is particularly interesting how the structural and residual differences of the same family determine the ATP hydrolysis mechanism and its effect on the overall function of these enzymes. Rad51, RadA and RecA are examples from this group of proteins, which fulfill particularly important roles in cellular functions: the repair of damaged DNA and the maintenance of genomic diversity. Despite the numerous studies, many details are still uncovered, especially the role of ATP hydrolysis and the description of the reaction mechanism at the atomic level. Computational biophysics provides an adequate set of tools to describe the atomic level structural differences and accurate energetics of the system. By using my experience in different quantum mechanical (QM/MM) and molecular dynamics simulations (MD), we aim to expand our current understanding of RecA enzymes, aiming to provide details on the coupling of reaction steps with the large scale motions. (2-3)

Related References

  1. T. Beke-Somfai, P. Lincoln, B. Nordén: Double-lock ratchet mechanism revealing the role of αSER-344 in FoF1 ATP synthase  Proc. Natl. Acad. Sci., U.S.A., 2011, 108, 4828-4833
  2. T. Beke-Somfai, P. Lincoln, B. Nordén: Rate of hydrolysis in ATP synthase is fine-tuned by α-subunit motif controlling active site conformation Proc. Natl. Acad. Sci., U.S.A., 2013, 110, 2117-2122
  3. A. Reymer, S. Babik, M. Takahashi B. Nordén, T. Beke-Somfai: ATP Hydrolysis in the RecA–DNA Filament Promotes Structural Changes at the Protein–DNA Interface Biochemistry, 2015, 54 (30), pp 4579–4582
Expertise: 
  • Circular and Linear dichroism
  • UV/Vis absorption spectroscopy
  • Computational biophysics
  • Sum-frequency generation spectroscopy
  • Supported lipid bilayers
  • Liposomal systems
  • Bicelles
Publications: