利伐沙班与β-酮酰[ACP]合成酶I的结合亲和力:寻找新的药效团

Q4 Chemistry
T. Lakhvich, V. M. Ryneiskaya
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引用次数: 0

摘要

利伐沙班作为恶唑烷酮系列的代表,对其β-酮酰[ACP]合成酶I的活性进行了硅研究。利用分子对接方法,确定了利伐沙班与蛋白质的结合位点。对于提供利伐沙班与蛋白质最高亲和力的位点(-10.26 kcal/mol),分析了4个以运行次数大于15次为特征的簇。发现配体在这些簇中的特定位置可以通过提供生理反应的机制改变。环境特征的微小变化可导致从以疏水相互作用为主的能量优势位置(BE = -10.26 kcal/mol)过渡到以亲水性相互作用为主的另一个位置(BE = -8.88 kcal/mol)。所讨论的动态转变可能引起生理反应。该研究结果具有很高的概率,证实了利伐沙班通过抑制真菌酸生物合成来实现抗细菌作用的特定机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
In silico Rivaroxaban binding affinity to β-ketoacyl[ACP]synthase I: search for new pharmacophore
The activity of Rivaroxaban as a representative of oxazolidinone series in relation to β-ketoacyl[ACP]synthase I has been studied in silico. Using the molecular docking methods, the binding sites of Rivaroxaban with protein have been identified. For the site providing the highest affinity of Rivaroxaban with protein (-10.26 kcal/mol), 4 clusters characterized by a number of runs greater than 15 have been analyzed. It was found that the specific position of the ligand within these clusters can be changed via mechanism providing a physiological response. Slight changes in the characteristics of the environment can lead to a transition from an energetically dominant position (BE = –10.26 kcal/mol) with predominantly hydrophobic interactions to another position (BE = –8.88 kcal/mol) with predominantly hydrophilic interactions. Dynamic transition discussed may cause a physiological response. The results of the study with a high degree of probability confirm the implementation of a specific mechanism of antimycobacterial action of Rivaroxaban through inhibition of the mycolate biosynthesis.
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来源期刊
CiteScore
0.30
自引率
0.00%
发文量
38
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