A computational perspective of molecular interactions through virtual screening, pharmacokinetic and dynamic prediction on ribosome toxin A chain and inhibitors of Ricinus communis

通过虚拟筛选、药代动力学和动力学预测,从计算角度研究蓖麻核糖体毒素A链及其抑制剂的分子相互作用

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Abstract

BACKGROUND: Ricin is considered to be one of the most deadly toxins and gained its favor as a bioweapon that has a serious social and biological impact, due to its widespread nature and abundant availability. The hazardous effects of this toxin in human being are seen in almost all parts of the organ system. The severe consequences of the toxin necessitate the need for developing potential inhibitors that can effectively block its interaction with the host system. MATERIALS AND METHODS: In order to identify potential inhibitors that can effectively block ricin, we employed various computational approaches. In this work, we computationally screened and analyzed 66 analogs and further tested their ADME/T profiles. From the kinetic and toxicity studies we selected six analogs that possessed appropriate pharmacokinetic and dynamic property. We have also performed a computational docking of these analogs with the target. RESULTS: On the basis of the dock scores and hydrogen bond interactions we have identified analog 64 to be the best interacting molecule. Molecule 64 seems to have stable interaction with the residues Tyr80, Arg180, and Val81. The pharmacophore feature that describes the key functional features of a molecule was also studied and presented. CONCLUSION: The pharmacophore features of the drugs provided suggests the key functional groups that can aid in the design and synthesis of more potential inhibitors.

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