Background: Chemotherapy and radiotherapy have negative effects on normal tissues and they are very expensive and lengthy treatments. These disadvantages have recently attracted researchers to the new methods that specifically affect cancerous tissues and have lower damage to normal tissues. One of these methods is the use of intelligent recombinant fusion toxin. The fusion toxin DTGCSF, which consists of linked Diphtheria Toxin (DT) and Granulocyte Colony Stimulate Factor (GCSF), was first studied by Chadwick et al. in 1993 where HATPL linker provided the linking sequence between GCSF and the 486 amino acid sequences of DT.

Methods: In this study, the fusion toxin DT389GCSF is evaluated for functional structure in silico. With the idea of the commercial fusion toxin of Ontak, the DT in this fusion protein is designed incomplete for 389 amino acids and is linked to the beginning of the GCSF cytokine via the SG4SM linker (DT389GCSF). The affinity of the DT389GCSF as a ligand with GCSF-R as receptor was compared with DT486GCSF as a ligand with GCSF-R as receptor. Both DT486GCSF and its receptor GCSF-R have been modeled by Easy Modeler2 software. Our fusion protein (DT389GCSF) and GCSF-R are modeled through Modeller software; all of the structures were confirmed by server MDWEB and VMD software. Then, the interaction studies between two proteins are done using protein-protein docking (HADDOCK 2.2 web server) for both the fusion protein in this study and DT486GCSF.

Results: The HADDOCK results demonstrate that the interaction of DT389GCSF with GCSF-R is very different and has a more powerful interaction than DT486GCSF with GCSF-R.

Conclusion: HADDOCK web server is operative tools for evaluation of protein–protein interactions, therefore, in silico study of DT389GCSF will help with studying the function and the structure of these molecules. Moreover, DT389GCSF may have important new therapeutic applications.

背景：化学疗法和放射疗法对正常组织有负面影响，是非常昂贵且漫长的治疗方法。这些缺点最近吸引了研究人员对新方法的关注，这些新方法专门影响癌变组织并且对正常组织的损害较小。这些方法之一是使用智能重组融合毒素。Chadwick等人首先研究了由连接的白喉毒素（DT）和粒细胞集落刺激因子（GCSF）组成的融合毒素DTGCSF。在1993年，HATPL接头提供了GCSF和DT的486个氨基酸序列之间的连接序列。

方法：在这项研究中，对融合毒素DT389GCSF的计算机功能结构进行了评估。根据Ontak的商业融合毒素的想法，此融合蛋白中的DT被设计为不完整的389个氨基酸，并通过SG4SM连接子（DT389GCSF）与GCSF细胞因子的开始相连。比较了以GCSF-R为受体的DT389GCSF作为配体的亲和力和以GCSF-R为受体的DT486GCSF作为配体的亲和力。DT486GCSF及其受体GCSF-R均已通过Easy Modeler2软件建模。我们的融合蛋白（DT389GCSF）和GCSF-R是通过Modeller软件建模的；服务器MDWEB和VMD软件确认了所有结构。然后，使用蛋白质-蛋白质对接（HADDOCK 2.2 Web服务器）对本研究中的融合蛋白和DT486GCSF进行两种蛋白质之间的相互作用研究。

结果：HADDOCK结果表明，DT389GCSF与GCSF-R的相互作用非常不同，并且与DT486GCSF与GCSF-R的相互作用更强。

结论：HADDOCK Web服务器是评估蛋白质间相互作用的有效工具，因此，对DT389GCSF进行计算机研究将有助于研究这些分子的功能和结构。此外，DT389GCSF可能具有重要的新治疗应用。