Significance of Knotted Structures for Function of Proteins and Nucleic Acids - September 17-21, 2014

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

- 57 -