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首页> 外文会议>IEEE International Conference on Bioinformatics and Biomedicine >Virtual screening, ADMET profiling, molecular docking and dynamics approaches to search for potent selective natural molecule based inhibitors against metallothionein-III to study Alzheimer's disease
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Virtual screening, ADMET profiling, molecular docking and dynamics approaches to search for potent selective natural molecule based inhibitors against metallothionein-III to study Alzheimer's disease

机译：虚拟筛选，ADMET分析，分子对接和动力学方法以寻找有效的基于选择性天然分子的金属硫蛋白-III抑制剂来研究阿尔茨海默氏病

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Motivation: Metallothionein-III (MT-III) displays neuro-inhibitory activity and is involved in the repair of neuronal damage. An altered expression level of MT-III suggests that it could be a mitigating factor in Alzheimer's disease (AD) neuronal dysfunction. Currently there are limited marketed drugs available against MT-III. The inhibitors are mostly pseudo-peptide based with limited ADMET. In our present study, available database InterBioScreen (natural compounds) was screened out for MT-III. Pharmacodynamics and pharmacokinetic studies were performed. Molecular docking and simulations of top hit molecules were performed to study complex stability. Results: Study reveals potent selective molecules that interact and form hydrogen bonds with amino acids Ser-6 and Lys-22 which are common to established melatonin inhibitors for MT-III. These include DMHMIO, MCA B and s27533 derivatives. The ADMET profiling was better with comparable interaction energy values. It includes properties like blood brain barrier, hepatotoxicity, druggability, mutagenicity and carcinogenicity. Molecular dynamics studies were performed to validate our findings.
机译：动机：金属硫蛋白-III（MT-III）具有神经抑制活性，并参与神经元损伤的修复。 MT-III表达水平的改变表明它可能是阿尔茨海默氏病（AD）神经元功能障碍的缓解因素。目前，针对MT-III的市售药物有限。抑制剂主要是基于假肽，具有有限的ADMET。在我们目前的研究中，从可用的数据库InterBioScreen（天然化合物）中筛选出了MT-III。进行了药效学和药代动力学研究。进行了分子对接和命中分子的模拟，以研究复杂的稳定性。结果：研究表明，有效的选择性分子可与氨基酸Ser-6和Lys-22相互作用并形成氢键，这是成熟的MT-III褪黑素抑制剂所共有的。这些包括DMHMIO，MCAB和s27533衍生物。在具有可比较的相互作用能值的情况下，ADMET分析更好。它包括诸如血脑屏障，肝毒性，可药物性，诱变性和致癌性等特性。进行了分子动力学研究以验证我们的发现。

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