In Silico Designing and Analysis of Inhibitors against Target Protein Identified through Host-Pathogen Protein Interactions in Malaria

Monika Samant, Nidhi Chadha, A. Tiwari, Y. Hasija
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引用次数: 6

Abstract

Malaria, a life-threatening blood disease, has been a major concern in the field of healthcare. One of the severe forms of malaria is caused by the parasite Plasmodium falciparum which is initiated through protein interactions of pathogen with the host proteins. It is essential to analyse the protein-protein interactions among the host and pathogen for better understanding of the process and characterizing specific molecular mechanisms involved in pathogen persistence and survival. In this study, a complete protein-protein interaction network of human host and Plasmodium falciparum has been generated by integration of the experimental data and computationally predicting interactions using the interolog method. The interacting proteins were filtered according to their biological significance and functional roles. α-tubulin was identified as a potential protein target and inhibitors were designed against it by modification of amiprophos methyl. Docking and binding affinity analysis showed two modified inhibitors exhibiting better docking scores of −10.5 kcal/mol and −10.43 kcal/mol and an improved binding affinity of −83.80 kJ/mol and −98.16 kJ/mol with the target. These inhibitors can further be tested and validated in vivo for their properties as an antimalarial drug.
通过疟疾宿主-病原体蛋白相互作用鉴定的靶蛋白抑制剂的计算机设计与分析
疟疾是一种危及生命的血液病,一直是保健领域的一个主要关切问题。恶性疟原虫(Plasmodium falciparum)是疟疾的一种严重形式,它是由病原体与宿主蛋白质的蛋白质相互作用引起的。分析宿主和病原体之间的蛋白质-蛋白质相互作用对于更好地理解这一过程和表征病原体持续和生存的特定分子机制至关重要。在本研究中,通过整合实验数据和使用interolog方法计算预测相互作用,生成了一个完整的人类宿主与恶性疟原虫蛋白质-蛋白质相互作用网络。根据相互作用蛋白的生物学意义和功能作用进行筛选。α-微管蛋白是一种潜在的蛋白靶点,并通过甲基氨丙磷的修饰设计了针对α-微管蛋白的抑制剂。对接和结合亲和力分析表明,两种修饰抑制剂的对接得分分别为−10.5 kcal/mol和−10.43 kcal/mol,与靶标的结合亲和力分别为−83.80 kJ/mol和−98.16 kJ/mol。这些抑制剂可以进一步在体内测试和验证其作为抗疟疾药物的特性。
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期刊介绍: International Journal of Medicinal Chemistry is a peer-reviewed, Open Access journal that publishes original research articles as well as review articles in all areas of chemistry associated with drug discovery, design, and synthesis. International Journal of Medicinal Chemistry is a peer-reviewed, Open Access journal that publishes original research articles as well as review articles in all areas of chemistry associated with drug discovery, design, and synthesis.
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