Ahmad Syed Sayeed, Akhtar Salman, Danish Rizvi Syed Mohd, Kamal Mohammad A, Sayeed Usman, Khan Mohd Kalim A, Siddiqui Mohd Haris, Arif Jamal M
Department of Bioengineering, Faculty of Engineering, Integral University, Lucknow, India.
Department of Pharmacology and Toxicology, College of Pharmacy, University of Hail, Hail, Saudi Arabia.
Curr Comput Aided Drug Des. 2017 Nov 10;13(4):311-318. doi: 10.2174/1573409913666170414123825.
The present study clarifies the molecular interactions of human BACE1 with novel natural ligands and also with the well-known ligand 2, 2, 4-trihydroxychalcone and Galangin for comparison.
The study of enzyme- ligands interaction is interesting, thus description of ligands binding to the active site of target molecule could be beneficial for better understanding the mechanism of the ligand on the target molecule.
Lipinski rule of five and docking study were performed between ligands and enzyme using 'Autodock4.2'.
It was found that hydrogen bond interactions play a significant role in the accurate positioning of ligands within the 'active site' of BACE1 to permit docking. Such information may aid to propose the BACE1 -inhibitors and is estimated to aid in the safe medical use of ligands. Selected ligands of BACE1 also inhibit the aggregated amyloid beta peptide. The aggregation of amyloid peptides Aβ1-42 may be responsible for AD.
Scope lies in the determination of the 3-dimensional structure of BACE1 and ligands complex by X-ray crystallography to certify the explained data. To validate the enzyme -ligands results, we considered 2, 2, 4-trihydroxychalconeas and Galangin as a positive control. Moreover, the current study verifies that ligands are more capable inhibitors of human BACE1 compared to positive control with reference to ΔG values.
本研究阐明了人类β-分泌酶1（BACE1）与新型天然配体以及与著名配体2,2,4-三羟基查耳酮和高良姜素之间的分子相互作用，以便进行比较。
酶-配体相互作用的研究很有趣，因此描述配体与靶分子活性位点的结合可能有助于更好地理解配体对靶分子的作用机制。
使用“Autodock4.2”对配体和酶进行了Lipinski五规则和对接研究。
发现氢键相互作用在配体在BACE1“活性位点”内的准确定位中起着重要作用，以允许对接。这些信息可能有助于提出BACE1抑制剂，并估计有助于配体的安全医学应用。BACE1的选定配体也抑制聚集的淀粉样β肽。淀粉样肽Aβ1-42的聚集可能是导致阿尔茨海默病的原因。
研究范围在于通过X射线晶体学确定BACE1与配体复合物的三维结构，以验证所解释的数据。为了验证酶-配体的结果，我们将2,2,4-三羟基查耳酮和高良姜素作为阳性对照。此外，本研究证实，就ΔG值而言，与阳性对照相比，配体是更有效的人类BACE1抑制剂。
