Received: 8 October 2018 | Revised: 8 January 2019 | Accepted: 14 January 2019 DOI: 10.1002/jcb.28519 RESEARCH ARTICLE Structural bioinformatics insights into the CARD‐CARD interaction mediated by the mitochondrial antiviral‐signaling protein of black carp Ajaya K. Rout 1 | Sheela R. Udgata 2 | Budheswar Dehury 3,4 | Smruti P. Pradhan 2 | Himanshu S. Swain 1 | Bijay K. Behera 1 | Basanta K. Das 1 1 Biotechnology Laboratory, ICAR—Central Inland Fisheries Research Institute, Kolkata, West Bengal, India 2 Department of Bioinformatics, Orissa University of Agriculture and Technology, Bhubaneswar, Odisha, India 3 Biomedical Informatics Centre, ICMR—Regional Medical Research Centre, Bhubaneswar, Odisha, India 4 Department of Chemistry, Technical University of Denmark, Kongens Lyngby, Denmark Correspondence Bijay K. Behera and Basanta K. Das, Biotechnology Laboratory, ICAR‐Central Inland Fisheries Research Institute, Barrackpore, Kolkata, West Bengal 700120, India. Email: beherabk18@yahoo.co.in; basantakumard@gmail.com Abstract The innate immune system offers the first line of defense against invading microbial pathogens through the recognition of conserved pathogen‐associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs). The host innate immune system through PRRs, the sensors for PAMPs, induces the production of cytokines. Among different families of PRRs, the retinoic acid‐ inducible gene I (RIG‐I)‐like receptors (RLRs), and its mitochondrial adaptor ie, the mitochondrial antiviral‐signaling (MAVS) protein, are crucial for RLR‐ triggered interferon (IFN) antiviral immunity. Recent studies have shown that the N‐terminal caspase recruitment domain (CARD) and transmembrane domain play a pivotal role in oligomerization of black carp MAVS (BcMAVS), crucial for the host innate immune response against viral invasion. In this study, we have used molecular modeling, docking, and molecular dynamics (MD) simulation approaches to shed molecular insights into the oligomeriza- tion mechanism of BcMAVS CARD . MD simulation and interaction analysis portrayed that the type‐I surface patches of BcMAVS CARD make the major contribution to the interaction. Moreover, the evidence from surface patches and critical residues involved in the said interaction is found to be similar to that of the human counterpart and requires further investigation for legitimacy. Altogether, our study provided crucial information on oligomeriza- tion of BcMAVS CARDs and might be helpful for clarifying the innate immune response against pathogens and downstream signaling in fishes. KEYWORDS CARD‐CARD interaction, caspase recruitment domains, mitochondrial antiviral‐signaling protein, molecular dynamics simulation, principal component analysis 1 | INTRODUCTION Innate immunity plays a pivotal role in immune defence against environmental disadvantages such as pathogen invasion. 1-3 The recognition of microbial pathogens, mediated by pattern recognition receptors (PRRs i.e., essential machinery of the innate immune system), is critical to the initiation of innate immune responses. 4 These PRRs recognize the conserved microbial compo- nents viz., pathogen‐associated molecular patterns (PAMPs) and damage‐associated molecular patterns (DAMPs), which induces subsequent host immunity J Cell Biochem. 2019;1-10. wileyonlinelibrary.com/journal/jcb © 2019 Wiley Periodicals, Inc. | 1