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Prions are protein infectious agents, which cause transmissible neurodegenerative diseases. Prion infection occurs as a result of the post-translational conversion of a normal cellular protein PrPC to a pathogenic and a prone to aggregation PrPSc isoform. PrPC consists of two domains: the unstructured N-terminal and the globular C-terminal. The N-domain includes two charged clusters (CC1 and CC2),a hydrophobic domain (HD), an octarepeat region (OR), and several proteolytic sites (α-, β- and γ-cleavages). Due to the high mobility of the N-domain, the structure of the full-length PrPC has not yet been obtained by experimental methods. In this work, we implemented de novo structure prediction and the molecular dynamics (MD) simulation method to study interactions between the functional domains of the full-length PrPC. The NMR solution structure of the C-domain was taken from the Protein Data Bank (ID code: 1dx0) and models of the N-domain were predicted in I-TASSER. Five top-scoring models were selected and merged with the C-domain to create five starting conformations for 300 ns-long MD simulations of PrPC in water. Interdomain contacts were analyzed using the CONAN package. According to our results, CC2 and α-cleavage regions of the N-domain are in contact with the C-domain for the majority of the simulation time, while OR and HD regions contribute to the interdomain interactions to a lesser extent. The contacts of the α-cleavage and HD are located closer to the C-terminus of the molecule (residues 180–200) and CC2 binds closer to the central part(residues 140–150). Our findings may be used for theoretical descriptions of pathological conformational transitions of the prion protein. The authors acknowledge funding from the Russian Science Foundation (grant 19-74-20055). Previously published in: Mamchur A.A. et al. (2020) Lobachevskii Journalof Mathematics 41, 1502-1508.