Comparison of computational and experimental results for intrinsically disordered proteins (IDPs)

Vojtěch Zapletal1,2, Arnošt Mládek2, Petr Louša2, Pavel Srb3, Vojtěch Kubáň1,2, Lukáš Žídek1,2, Jozef Hritz2

1NCBR, Faculty of Science, Masaryk University, Kamenice 5, 62500 Brno, Czech Republic,

2CEITEC MU, Masaryk University, Kamenice 5, 62500 Brno, Czech Republic, 

3Institute of Organic Chemistry and Biochemistry ASCR, v.v.i., Flemingovo nám. 2, 16610 Praha 6, Czech Republic

The discovery of intrinsically disordered proteins (IDPs) has challenged the traditional protein structure paradigm, that protein function depends on a fixed three-dimensional structure. The various branches of structural biology developed new approaches for the study of IDPs which are compared in this work.  Delta subunit of RNA polymerase from Bacillus subtilis and a regulatory domain of human tyrosine hydroxylase 1 were chosen for studies because they consist of structured and disordered regions of a similar size. RNA polymerase plays a fundamental role in the process of protein synthesis and tyrosine hydroxylase catalyzes hydroxylation of L-tyrosine to L-DOPA and it is a key enzyme in biosynthesis of dopamine. Experimental data such as NMR chemical shifts, residual dipolar coupling (RDC), paramagnetic relaxation enhancement (PRE), and SAXS data are compared with the theoretical values calculated from the MD trajectory. This comparison can be used to determine the accuracy of the calculated structural ensembles and to guide design of additional experiments.

The project is financed from the SoMoPro II programme. The research leading to this invention has acquired a financial grant from the People Programme (Marie Curie action) of the Seventh Framework Programme of EU according to the REA Grant Agreement No. 291782. The research is further co-financed by the South-Moravian Region. The article/paper reflects only the author´s views and the Union is not liable for any use that may be made of the information contained therein. In addition, this work was also supported by Czech Science Foundation (15-34684L). The computational simulations were realized in the National Supercomputing Center IT4Innovations, which is supported by The Ministry of Education, Youth and Sports from the Large Infrastructures for Research, Experimental Development and Innovations project „IT4Innovations National Supercomputing Center – LM2015070“. Further computational resources were provided by the MetaCentrum under the program LM2015042 and the CERIT Scientific Cloud under the program LM2015085, provided under the programme "Projects of Large Infrastructure for Research, Development, and Innovations". This research was carried out under the project CEITEC 2020 (LQ1601) with financial support from the Ministry of Education, Youth and Sports of the Czech Republic under the National Sustainability Programme II. This work was supported by Czech Science Foundation, grant number GA 13-16842S.