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Co-evolution analysis to predict protein-protein interactions within the Influenza virus envelope Ramil R. MINTAEV
Department of Bioengineering and Bioinformatics, Moscow State University, Leninskie Gory 1-37, Moscow 119991, Russia, ramil.mintaev@gmail.com

Andrei V. ALEXEEVSKI
Department of Bioengineering and Bioinformatics & Belozersky Institute of Physico-Chemical Biology, Moscow State University, Leninskie Gory 1-37 & 1-40, Moscow 119991, Russia, aba@belozersky.msu.ru

Larisa V. KORDYUKOVA
Belozersky Institute of Physico-Chemical Biology, Moscow State University, Leninskie Gory 1-40, Moscow 119991, Russia, kord@belozersky.msu.ru

Influenza A virus belongs to Orthomyxo viridae family o f enveloped viruses. Three transmembrane proteins are incorporated into the viral envelope: the surface glycoproteins hemagglut inin (HA) and neuraminidase (NA) that fulfill the virio ns' attachment and cell receptor destroying function, respect ively, and a minor protein M2 facilitat ing virio ns budding and providing a proton input into the virio n's interior. Major structural protein M1 underlies the viral lipid membrane. There are indirect experimental data confirming the existence o f protein-protein interactions within the influenza virus envelope. Yet, there is no data available regarding the amino acids residues participat ing in those interactions. To predict amino acid interactions for pairs of envelope proteins, we (1) calculated the so-called Direct Informat ion (DI) based on an approach of [Marks et al., PLoS One 6(12) 2011]. To dist inguish true co-evolut ion couplings from the noisy set of correlat ions observed according to the mult iple sequence alignment, the authors propose computing a set of direct residue couplings. Second, among those amino acid residue pairs possessing DI > 0,1 we have manually chosen those located within the topographically co mpat ible protein domains. Next, we calculated amino acid pair frequencies for our candidates. Last, we checked whether the amino acid residues within a pair are compat ible regarding their phys icochemical properties. We have found 2 amino acid (a.o.) pairs for the HA-M1 protein pair, 1 and 3 a.o. pairs for the HA-M2 and M1-M2 pairs, respectively (in total, 6 a.o. pairs, Fig. 1). No a.o. pairs were found for the HA-NA pair because of extreme conservat ion of the NA cytoplasmic tail.


Fig. 1. Amino acid residues predicted to participate in the protein-protein interactions. According to our predict ions, a hypothetical model of protein-protein interact ions within the viral envelope was proposed (Fig.2). Noteworthy, the interactions may not be realized simultaneously since there is different copying of the proteins wit hin the virio n.

Fig.2. Hypothetical model of the protein-protein interactions within the viral envelope. This work was supported by RFBR grants 11-04-91340-NNIO, 13-04-00290.