Virtual Screening of Flavonoids against Plasmodium vivax Duffy Binding Protein Utilizing Molecular Docking and Molecular Dynamic Simulation.

IF 1.5 4区医学 Q4 CHEMISTRY, MEDICINAL Current computer-aided drug design Pub Date : 2024-01-01 DOI:10.2174/1573409919666230626140339

Muhammad Yasir, Jinyoung Park, Eun-Taek Han, Won Sun Park, Jin-Hee Han, Yong-Soo Kwon, Hee-Jae Lee, Wanjoo Chun

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Abstract

Background: Plasmodium vivax (P. vivax) is one of the highly prevalent human malaria parasites. Due to the presence of extravascular reservoirs, P. vivax is extremely challenging to manage and eradicate. Traditionally, flavonoids have been widely used to combat various diseases. Recently, biflavonoids were discovered to be effective against Plasmodium falciparum.

Methods: In this study, in silico approaches were utilized to inhibit Duffy binding protein (DBP), responsible for Plasmodium invasion into red blood cells (RBC). The interaction of flavonoid molecules with the Duffy antigen receptor for chemokines (DARC) binding site of DBP was investigated using a molecular docking approach. Furthermore, molecular dynamic simulation studies were carried out to study the stability of top-docked complexes.

Results: The results showed the effectiveness of flavonoids, such as daidzein, genistein, kaempferol, and quercetin, in the DBP binding site. These flavonoids were found to bind in the active region of DBP. Furthermore, the stability of these four ligands was maintained throughout the 50 ns simulation, maintaining stable hydrogen bond formation with the active site residues of DBP.

Conclusion: The present study suggests that flavonoids might be good candidates and novel agents against DBP-mediated RBC invasion of P. vivax and can be further analyzed in in vitro studies.

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利用分子对接和分子动力学模拟虚拟筛选针对间日疟原虫达菲结合蛋白的黄酮类化合物

背景：间日疟原虫（P. vivax）是高度流行的人类疟疾寄生虫之一。由于存在血管外储库，间日疟原虫的管理和根除极具挑战性。传统上，黄酮类化合物被广泛用于防治各种疾病。最近，人们发现双黄酮类化合物对恶性疟原虫有效：在这项研究中，我们利用硅学方法来抑制达菲结合蛋白（DBP），它是疟原虫侵入红细胞（RBC）的罪魁祸首。利用分子对接方法研究了黄酮类分子与DBP的达菲抗原受体趋化因子（DARC）结合位点的相互作用。此外，还进行了分子动态模拟研究，以研究顶级对接复合物的稳定性：结果：研究结果表明，黄酮类化合物（如大豆苷、染料木苷、山奈酚和槲皮素）在 DBP 结合位点上的有效性。这些类黄酮被发现结合在 DBP 的活性区。此外，这四种配体在整个 50 ns 模拟过程中保持稳定，与 DBP 的活性位点残基保持稳定的氢键形成：本研究表明，类黄酮可能是对抗由 DBP 介导的间日疟原虫 RBC 侵袭的良好候选药物和新型药物，可在体外研究中进行进一步分析。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current computer-aided drug design 医学-计算机：跨学科应用

CiteScore

3.70

自引率

5.90%

发文量

审稿时长

>12 weeks

期刊介绍： Aims & Scope Current Computer-Aided Drug Design aims to publish all the latest developments in drug design based on computational techniques. The field of computer-aided drug design has had extensive impact in the area of drug design. Current Computer-Aided Drug Design is an essential journal for all medicinal chemists who wish to be kept informed and up-to-date with all the latest and important developments in computer-aided methodologies and their applications in drug discovery. Each issue contains a series of timely, in-depth reviews, original research articles and letter articles written by leaders in the field, covering a range of computational techniques for drug design, screening, ADME studies, theoretical chemistry; computational chemistry; computer and molecular graphics; molecular modeling; protein engineering; drug design; expert systems; general structure-property relationships; molecular dynamics; chemical database development and usage etc., providing excellent rationales for drug development.