Sefid Fateme, Rasooli Iraj, Payandeh Zahra
Department of Biology, Shahed University, Tehran-Qom Express Way, Tehran 3319118651, Iran.
Department of Biology, Shahed University, Tehran-Qom Express Way, Tehran 3319118651, Iran; Molecular Microbiology Research Center, Shahed University, Tehran, Iran.
J Theor Biol. 2016 May 21;397:43-51. doi: 10.1016/j.jtbi.2016.02.015. Epub 2016 Feb 18.
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.
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.
We identified the amino acids involved in antigen-VHH interactions. Some functional conserved 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.
VHH或单域抗体（sdAb）正被研究用于癌症、感染及其他疾病的治疗应用。在我们之前的研究中，我们表达并制备了一种针对鲍曼不动杆菌生物膜相关蛋白（Bap）保守区域的可溶性VHH。本研究旨在预测受体和配体的二维和三维结构以及参与它们相互作用的残基。
除了从头计算法，还采用了其他合理方法，如同源建模和穿线法来获得三维结构。对于同源建模，对序列运行BLAST以找到最佳模板。在该结构上进行口袋检测、鉴定VHH三维结构中功能和结构上重要的残基以及确定其裂隙和配体结合位点。ZDOCK对接服务器预测了作为抗原的Bap选定区域与作为抗体的VHH结构之间在平移和旋转空间中的所有可能结合模式。
我们确定了参与抗原-VHH相互作用的氨基酸。鉴定出了位于参与配体结合位点的最大裂隙中的一些功能保守残基。似乎这些氨基酸参与了抗原-VHH相互作用。
