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Conformational changes in proteins
and peptides are essential for their biological
function. One of the most drastic and most essential
conformational changes is the protein folding
reaction. The rate at which a protein can explore
conformational space during folding is limited
by intrachain diffusion processes. The maximum
rate for conformational changes leading to specific
intramolecular interactions is set by the process
of intramolecular contact formation. To understand
the dynamics in unfolded polypeptide chains we
are studying contact formation between individual
amino acid residues using diffusion controlled
triplet-triplet energy transfer (TTET).[1] Combination
of femtoseconds and nanoseconds laserflash experiments
allows us to monitor intrachain contact formation
on the 1 ps to 100 ?s time-scale. Recent experiments
focused on the dynamics in unfolded model polypeptide
chains and in fragments derived from natural proteins.
[2; 3] Our current research focuses on the study
of chain dynamics in the unfolded state of full-length
proteins and in folding intermediates. This will
allow to asses the role of long-range interactions
in dynamics of unfolded proteins and to elucidate
structural and dynamic properties of different
states along the reaction coordinate for the protein
folding reactions. A special emphasis is put on
the role of protein-solvent interactions. The
projects are highly interdisciplinary by combining
methods and concepts from Biochemistry, Chemistry
and Physics.
- Bieri, O., Wirz, J., Hellrung, B., Schutkowski,
M., Drewello, M. & Kiefhaber, T. (1999).
The speed limit for protein folding measured
by triplet-triplet energy transfer. Proc.
Natl. Acad. Sci. USA 96, 9597-9601.
- Fierz, B. & Kiefhaber, T. (2005). Dynamics
of unfolded polypeptide chains. In Protein Folding
Handbook (Buchner, J. & Kiefhaber, T., eds.),
pp. 805-851. WILEY-VCH, Weinheim.
- Fierz, B., Satzger, H., Root, C., Gilch, P.,
Zinth, W. & Kiefhaber, T. (2007). Loop Formation
in Unfolded Polypeptide Chains on the Picoseconds
to Microseconds Time Scale. Proc. Natl.
Acad. Sci. USA 104, 2163-2168.
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