Homology modeling of a Camelid antibody fragment against a conserved region of Acinetobacter baumannii biofilm associated protein (Bap) Q2 Fateme Sefid a , Iraj Rasooli a,b,n , Zahra Payandeh a Q1 a Department of Biology, Shahed University, Tehran-Qom Express Way, Tehran 3319118651, Iran b Molecular Microbiology Research Center, Shahed University, Tehran, Iran HIGHLIGHTS  Homology modeling of a VHH against conserved region of A. baumannii Bap was studied.  Important VHH 3D structure residues and its clefts, ligand binding site were studied.  Binding modes between Bap as an antigen and the VHH as an antibody were predicted.  Amino acids involved in antigen-VHH interactions were identified.  Functional residues in the largest cleft acting in ligand binding were identified. article info Article history: Received 31 January 2015 Received in revised form 26 December 2015 Accepted 10 February 2016 Keywords: VHH Acinetobacter baumannii Biofilm associated protein Single-domain antibody abstract Background: VHH or the single-domain antibodies (sdAb), are studied for therapeutic applications in cancers, infections and other diseases. In our previous study, we expressed and produced a soluble VHH against a conserved region of Acinetobacter baumannii biofilm associated protein (Bap). The present study was undertaken to predict the 2D and 3D structure of the receptor and ligand as well as residues involved in their interactions. Methods and findings: Apart from ab initio, other rational methods such as homology modeling and threading were invoked to achieve the 3D structures. For homology modeling, BLAST was run on the sequences in order to find the best templates. Pocket detection and identification of functionally and structurally important residues of VHH 3D structure as well as determination of its clefts and ligand binding site were carried out on the structure. ZDOCK docking server predicted all possible binding modes in the translational and rotational space between the selected region of Bap as an antigen and the VHH structure as an antibody. Conclusion: We identified the amino acids involved in antigen-VHH interactions. Some functional con- served residues located in the largest cleft that participate in ligand binding site are identified. It seems that these amino acids are involved in antigen-VHH interactions. & 2016 Published by Elsevier Ltd. 1. Introduction Acinetobacter baumannii is a multidrug-resistant pathogen associated with hospital outbreaks across the world, particularly in the intensive care unit. The ability of A. baumannii to survive in the hospital environment for long periods is linked to its antibiotic resistance and its capacity to form biofilms which give enhanced resistance to antimicrobial stressors, antibiotics or cleaning pro- cedures (Mack et al., 2000; Joo and Otto, 2012; Gaddy and Actis, 2009). Because therapeutic options are limited for this organism alternative treatments should be evaluated. Monoclonal or poly- clonal antibodies have been reported to target surface-attached molecules such as Biofilm-associated proteins. Recent studies have shown that antibodies can strongly inhibit biofilm formation. In this regard, it has been demonstrated that specific antibody actions involved interference with capsular polysaccharide release from fungal cell and it can inhibit biofilm formation (Martinez and Casadevall, 2005). Other researchers reported the development of monoclonal antibodies (MAbs) specific to accumulation-associated 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 Contents lists available at ScienceDirect journal homepage: www.elsevier.com/locate/yjtbi Journal of Theoretical Biology http://dx.doi.org/10.1016/j.jtbi.2016.02.015 0022-5193/& 2016 Published by Elsevier Ltd. n Correspon Q3 dence to: Biology Department and Molecular Microbiology Research Center, Shahed University, Tehran-Qom Express Way, Tehran 3319118651, Iran. Tel.: þ98 21 51212200; fax: þ98 21 51212201. E-mail address: rasooli@shahed.ac.ir (I. Rasooli). Please cite this article as: Sefid, F., et al., Homology modeling of a Camelid antibody fragment against a conserved region of Acinetobacter baumannii biofilm associated protein (Bap). J. Theor. Biol. (2016), http://dx.doi.org/10.1016/j.jtbi.2016.02.015i Journal of Theoretical Biology ∎ (∎∎∎∎) ∎∎∎–∎∎∎