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首页> 外文期刊>Journal of Biomolecular Structure and Dynamics >Viper venom hyaluronidase and its potential inhibitor analysis: a multipronged computational investigation
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Viper venom hyaluronidase and its potential inhibitor analysis: a multipronged computational investigation

机译：VIPER毒液透明质酸酶及其潜在抑制剂分析：多重计算调查

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Viper venom hyaluronidase (VV-HYA) inhibitors have long been used as therapeutic agents for arresting the local and systemic effects caused during its envenomation. Henceforth, to understand its structural features and also to identify the best potential inhibitor against it the present computational study was undertaken. Structure-based homology modeling of VV-HYA followed by its docking and free energy-based ranking analysis of ligand, the MD simulations of the lead complex was also performed. The sequence analysis and homology modeling of VV-HYA revealed a distorted (/)(8) folding as in the case of hydrolases family of proteins. Molecular docking of the resultant 3D structure of VV-HYA with known inhibitors (compounds 1-25) revealed the importance of molecular recognition of hotspot residues (Tyr 75, Arg 288, and Trp 321) other than that of the active site residues. It also revealed that Trp 321 of VV-HYA is highly important for mediating - interactions with ligands. In addition, the molecular docking and comparative free energy binding analysis was investigated for the VV-HYA inhibitors (compounds 1-25). Both molecular docking and relative free energy binding analysis clearly confirmed the identification of sodium chromoglycate (compound 1) as the best potential inhibitor against VV-HYA. Molecular dynamics simulations additionally confirmed the stability of their binding interactions. Further, the information obtained from this work is believed to serve as an impetus for future rational designing of new novel VV-HYA inhibitors with improved activity and selectivity.
机译：VIPER毒液透明质酸酶（VV-HYA）抑制剂长期被用作治疗剂，用于阻止在其envenomation期间引起的局部和全身效应。从此，以了解其结构特征，也是为了识别目前的计算研究的最佳潜在抑制剂。基于结构的vv-hya的同源性建模，然后进行其对接和基于空闲的配体排名分析，也进行了引入络合物的MD模拟。 VV-HYA的序列分析和同源性建模显示，在水解蛋白质家族的情况下，扭曲（/）（8）折叠。具有已知抑制剂的VV-HYA所得3D结构的分子对接（化合物1-25）揭示了除活性位点残基之外的热点残基（TYR 75，ARC 288和TRP 321）的分子识别的重要性。它还显示VV-HYA的TRP 321对于介导 - 与配体相互作用非常重要。此外，研究了用于VV-HYA抑制剂的分子对接和比较自由能结合分析（化合物1-25）。分子对接和相对的自由能结合分析清楚地证实了色色温糖（化合物1）作为对抗VV-HYA的最佳潜在抑制剂的鉴定。分子动力学模拟另外证实了它们结合相互作用的稳定性。此外，从该工作获得的信息被认为是具有改善的活动和选择性的新新型VV-Hya抑制剂的未来合理设计的推动力。

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