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university of tampere: faculty of medicine and life sciences: research: markku kulomaa - molecular biotechnology:
Lääketieteen ja biotieteiden tiedekuntaUniversity of TampereLääketieteen ja biotieteiden tiedekunta
Markku Kulomaa - Molecular Biotechnology

Projects

Avidin ligand binding engineering

Dynamic models of molecular interactions

Investigators:

Paldanius
Niederhauser
Hiltunen
Kulomaa
Takkinen (VTT Oulu/Espoo)
Hytönen

Avidins are proteins naturally binding H-vitamin, biotin. In our approach, avidin proteins are engineered to achieve tailored ligand binding properties. In addition to rational mutagenesis, proteins are also subjected to DNA shuffling (Stemmer 1994). After mutagenesis mutants with desired properties will be selected with powerful selection technique called phage display (Smith 1985). This technology can be also called as directed evolution. The developed novel ligand binding molecules can be used as an alternative for antibodies for therapy and diagnostics (Binz, Amstutz & Pluckthun 2005).

Funding:

Academy of Finland
TEKES

References:

Binz, H.K., Amstutz, P. & Pluckthun, A. 2005, "Engineering novel binding proteins from nonimmunoglobulin domains", Nature biotechnology, vol. 23, no. 10, pp. 1257-1268.

Smith, G.P. 1985, "Filamentous fusion phage: novel expression vectors that display cloned antigens on the virion surface", Science, vol. 228, no. 4705, pp. 1315-1317.

Stemmer, W.P. 1994, "DNA shuffling by random fragmentation and reassembly: in vitro recombination for molecular evolution", Proc Natl Acad Sci U S A, vol. 91, no. 22, pp. 10747-1051.

Chicken avidin (PDB 2AVI) shown in cartoon model

Investigators:

Kukkurainen
Valjakka
Hytönen

We use computational biology to create dynamic models of protein-ligand complexes in order to improve our understanding of their biological function, but also to manipulate the complexes to make them suitable for biotechnical use. Computational methods are used to design mutations and to interpret experimental results. The advantage of the computational approach as compared to experimental research is that it allows screening of wide arrays of interaction pairs and makes it possible to study atomic details of the complexes.

Biotin in the binding pockets of a rhizavidin model. Position of the ligand relative to the protein at differents time points of a 1 ns simulation is shown.


References:

Humphrey W, Dalke A, Schulten K. VMD - Visual Molecular Dynamics. J Mol Graphics, 1996, 14: 33-38.

Hytönen VP, Vogel V. How force might activate talin's vinculin binding sites: SMD reveals a structural mechanism. PLoS Comput Biol, 2008, 4(2):e24.

Phillips JC, Braun R, Wang W, Gumbart J, Tajkhorshid E, Villa E, Chipot C, Skeel RD, Kale L, Schulten K. Scalable molecular dynamics with NAMD. J Comput Chem, 2005, 26: 1781-1802.

Collaborators:

Viola Vogel (ETH Zürich, Switzerland) Bernhard Wehrle-Haller (University of Geneva, Switzerland) Mikael Peräkylä (University of Kuopio, Finland) Tomi Airenne (Åbo Akademi University, Turku, Finland)

 

 
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Last update: 6.11.2011 10.14 Muokkaa

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