Singh Surya Pratap, Gupta Dwijendra
Center of Bioinformatics, University of Allahabad, Allahabad 211002, India; Department of Bioscience and Biotechnology, Banasthali University, Banasthali 304022, India.
Center of Bioinformatics, University of Allahabad, Allahabad 211002, India; Department of Biochemistry, University of Allahabad, Allahabad 211002, India.
Comput Biol Chem. 2017 Jun;68:224-230. doi: 10.1016/j.compbiolchem.2017.04.002. Epub 2017 Apr 12.
Alzheimer's disease (AD) is a progressive neurodegenerative disease of central nervous system among elderly people. Human acetylcholinesterase (hAChE), an important enzyme in neuronal signaling, is responsible for the degradation of acetylcholine which in turn prevents the post synaptic signal transmissions. hAChE has been an attractive target of drug discovery for the search of therapeutics against AD. In the recent past hAChE has become hot target for the investigation of new potential therapeutics. We performed virtual screening of entire database against hAChE. Further, the extra precision molecular docking was carried out to refine the docking results and the best complex was passed for molecular dynamics simulations in order of understanding the hAChE dynamics and its behavior in complex with the ligand which corroborate the outcomes of virtual screening. This also provides binding free energy data that establishes the ligands efficiency for inhibiting hAChE. The computational findings discussed in this paper provide initial information of inhibitory effects of ligand, (drugbank entry DB00983), over hAChE.
阿尔茨海默病（AD）是老年人中枢神经系统的一种进行性神经退行性疾病。人乙酰胆碱酯酶（hAChE）是神经元信号传导中的一种重要酶，负责乙酰胆碱的降解，进而阻止突触后信号传递。hAChE一直是药物研发中寻找AD治疗药物的一个有吸引力的靶点。最近，hAChE已成为研究新的潜在治疗方法的热门靶点。我们对整个数据库进行了针对hAChE的虚拟筛选。此外，进行了额外精度的分子对接以优化对接结果，并将最佳复合物用于分子动力学模拟，以了解hAChE的动力学及其与配体结合时的行为，这证实了虚拟筛选的结果。这还提供了结合自由能数据，确定了配体抑制hAChE的效率。本文讨论的计算结果提供了配体（药物银行条目DB00983）对hAChE抑制作用的初步信息。
