Significance of Knotted Structures for Function of Proteins and Nucleic Acids
Poster Session I
8 – POS
Board 8
How to Detect Experimentally Knots in Proteins
Paweł Dąbrowski-Tumański
1
and Joanna I. Sułkowska
1,2
1
Faculty of Chemistry, University of Warsaw, Warsaw, Poland.
2
Centre of New Technologies,
University of Warsaw, Warsaw, Poland
Proteins that contains knots in their native states [1] are related to surprisingly many human
diseases, e.g. Parkinson disease. They are also targets for psychostimulants, anti-depressants and
other drugs in depression, mood abnormalities, and other neurological disorders. It has been
proposed, that the knots provide some sort of stabilization by holding together certain domains of
the protein. Nevertheless, in majority of cases we are unable to determine a function of a knot.
An important obstacle to find a function of knots in proteins is the lack of experimental tools to
detect unfolded and unknotted states of a protein.
Here, based on numerical simulations, we propose how knots in proteins could be detected
experimentally, for example using the FRET technique. We present the optimal reaction
coordinate (a distance between two distinct aminoacids) to distinguish between the unfolded
unknotted and the unfolded knotted states. Moreover we study the way the protein unknots and
compare it with the way it knots based on a protein with trefoil knot (pdb code 2efv [2]. In our
simulations we determine a knot type using implementation of Alexander or HOMFLY
polynomial.
References:
[1] J. I. Sulkowska, E.J. Rawdon, K.C. Millett, J. N. Onuchic, A. Stasiak, Conservation of
complex knotting and slipknotting patterns in proteins, PNAS, 2012, 109 (26), pp. E1715–E1723
[2] J.K. Noel, J.N. Onuchic, J.I. Sulkowska, Knotting a protein in explicit solvent,
The Journal of Physical Chemistry Letters, 2013, 4 (21), 3570-3573
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