Molecular modeling and docking characterization of Dectin-1 (PAMP) receptor of Bubalus bubalis Brijesh S. Yadav a, ⁎, Vijay Tripathi c , Ajeet Kumar a , Md. Faheem Khan d , Abhijit Barate e , Ajay Kumar b , Bhaskar Sharma a a Division of Biochemistry, Indian Veterinary Research Institute, Izatnagar 243122, India b Division of Animal Biotechnology, Indian Veterinary Research Institute, Izatnagar 243122, India c Centre of Bioinformatics IIDS, University of Allahabad, Allahabad 211002, India d Department of Plant Science, M.J.P. Rohilkhand University, Bareilly 243122, India e Laboratory of Infectious Diseases & Vaccine Development, Kangwon National University, South Korea abstract article info Article history: Received 11 September 2011 and in revised form 14 September 2011 Available online 08 October 2011 Keywords: Dectin-1 receptor β-glucan Homology modeling Docking Dectin-1, is a type II transmembrane receptor protein which contains a single extracellular CTLD (C-type lec- tin domain), stalk, transmembrane domain and an ITAM (immunoreceptor tyrosine-based activation motifs) in its cytoplasmic tail. Dectin-1 has the ability to recognize fungal β-glucans, which are carbohydrate PAMPs found predominantly in fungal cell walls. The recognition of fungal β-glucans by Dectin-1 helps in a variety of cellular responses, like host protection, such as fungal uptake and killing, and the production of inflammatory cytokines and chemokines. In this study we predicted the 3D (three dimensional) structure of Dectin-1 receptor based on homology modeling using MODELLER 9v8 software. The TMHMM server was used for the prediction of transmembrane helices. DALI, PROFUNC, Q-Site Finder, PINTS servers and PASS software used for the prediction of functional sites in the modeled Dectin-1 receptor. The docking investigation of Dectin-1 receptor with β-glucan suggests that ASP150, ASP113, GLY106, and GLU196 amino acids are the catalytic residues which form a shallow groove in the protein surface and bind to ligand β-glucan. We hope that this work will help in in-silico screening, structure-based design, and in understanding the structural basis of ligand binding to the Dectin-1 receptor. © 2011 Elsevier Inc. All rights reserved. Introduction The rate of new discovered protein sequences is very high, whereas, the rate of detailed structural information about proteins by X-ray diffraction or nuclear magnetic resonance spectroscopy (NMR) is far less. Thus, there is an essential need for theoretical methods to predict protein structure from sequences. Presently, many protein 3D structures are predicted by homology modeling. This method involves aligning a desired protein to one or more nonredundant homologous sequences of a template protein and evaluating the alignment using a scoring matrix. Differing side chains can be added from a side chain library according to known side chain preferences, followed by extensive energy minimization to elimi- nate steric clashes (Schwede et al., 2000). The predicted three- dimensional (3 D) structure of proteins using the homology model- ing method is imprecise. Considering the uncertainties involved in homology modeling, it is imperative that the initial 3D model be verified to assess its structural integrity and biological relevance before it is used in structure-based drug design projects (Marti et al., 2003). Refining of homology models is usually based either on energy minimization, limited conformational sampling using molecular dynamics (MD) in conjunction with a detailed force field, or more extensive sampling using simplified force fields (Schonbrun et al., 2002). Many endogenous and exogenous ligands for Dectin-1 have been reported, but the receptors mainly recognize a ligand known as fun- gal β-glucans. These are carbohydrate PAMPs predominantly present in fungal cell walls. They consist primarily of (1–3)-β-D-linked poly- mer backbones with (1–6)-β-linked side chains of varying length and distribution (Romani, 2004, Tsoni and Brown, 2008). Dectin-1 recep- tor has three parts: a single extracellular C-type lectin-like domain (CTLD), a transmembrane region, and a cytoplasmic tail that contains a single tyrosine-based activation motif. Its alternative splicing gener- ates two major Dectin-1 isoforms and a number of minor isoforms. The two major isoforms bind to β-glucan, but differ in the presence or absence of a stalk region and their ability to bind and induce Experimental and Molecular Pathology 92 (2012) 7–12 ⁎ Corresponding author. E-mail address: brijeshbioinfo@gmail.com (B.S. Yadav). 0014-4800/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.yexmp.2011.09.018 Contents lists available at SciVerse ScienceDirect Experimental and Molecular Pathology journal homepage: www.elsevier.com/locate/yexmp