Mostefai Noria, Cherif Fatima Yahia, Hosen Md Najmul, Ouici Houari B, Brahim Houari, Guendouzi Abdelmadjid, Belkhiri Lotfi, Guendouzi Abdelkrim, Alharbi Hanan M, Jawi Motasim, Hassan Hesham M, Al-Emam Ahmed
Laboratory of Chemistry: Synthesis, Properties and Applications, Faculty of Science and Technology, University of Saida, Algeria.
University of Science and Technology Chittagong (USTC), Bangladesh; Computational Biology Research Laboratory, Department of Pharmacy, Daffodil International University, Dhaka, Bangladesh.
Talanta. 2025 May 1;286:127370. doi: 10.1016/j.talanta.2024.127370. Epub 2024 Dec 9.
Complexing medications with cyclodextrins can enhance their solubility and stability. In this study, we investigated the host-guest complexation between Tetrahydrocurcumin (THC) and Hydroxypropyl-β-Cyclodextrin (HP-β-CD) using density functional theory (DFT) at the B3LYP-D3/TPZ level of theory in two possible orientations. To determine the reactive sites in both complexes for electrophilic and nucleophilic attacks, we calculated and interpreted the binding energy, HOMO and LUMO orbitals, global chemical reactivity descriptors, natural bond orbital (NBO) analysis, and Fukui indices. The results indicate that Orientation A is energetically more favorable than Orientation B. Non-covalent interactions (NCI) were analyzed using reduced density gradient (RDG) approaches, providing detailed insights into host-guest interactions, including hydrogen bonding and van der Waals forces. To further assess stability, we conducted 1000 ns molecular dynamics (MD) simulations and analyzed the root mean square deviations (RMSD) for systems containing 1, 2, and 10 complexes. The RMSD analysis confirmed the stability of the systems, with average RMSD values of 2.01, 3.21, and 4.29 Å, respectively. In the second part of this study, we examined the interaction between THC and the target protein Acetylcholinesterase (E.C. 3.1.1.7) with PDB ID 1QTI. Molecular docking was performed to identify the binding modes and interaction energies of the THC-protein complex. Subsequently, 1000 ns MD simulations were conducted to assess the stability and dynamic behavior of the THC-protein complex over an extended period. The analysis provided valuable insights into the binding interactions and stability of THC with the target protein, further confirming its potential as a therapeutic agent.
将药物与环糊精络合可以提高其溶解度和稳定性。在本研究中，我们使用密度泛函理论（DFT）在B3LYP-D3/TPZ理论水平下，对四氢姜黄素（THC）和羟丙基-β-环糊精（HP-β-CD）在两种可能的取向下的主客体络合进行了研究。为了确定两种络合物中亲电和亲核攻击的反应位点，我们计算并解释了结合能、最高占据分子轨道（HOMO）和最低未占据分子轨道（LUMO）、全局化学反应性描述符、自然键轨道（NBO）分析以及福井指数。结果表明，取向A在能量上比取向B更有利。使用密度降低梯度（RDG）方法分析了非共价相互作用（NCI），提供了对主客体相互作用的详细见解，包括氢键和范德华力。为了进一步评估稳定性，我们进行了1000纳秒的分子动力学（MD）模拟，并分析了包含1、2和10个络合物的系统的均方根偏差（RMSD）。RMSD分析证实了系统的稳定性，平均RMSD值分别为2.01、3.21和4.29埃。在本研究的第二部分，我们研究了THC与PDB ID为1QTI的靶蛋白乙酰胆碱酯酶（E.C. 3.1.1.7）之间的相互作用。进行了分子对接以确定THC-蛋白质复合物的结合模式和相互作用能。随后，进行了1000纳秒的MD模拟，以评估THC-蛋白质复合物在较长时间内的稳定性和动态行为。该分析为THC与靶蛋白的结合相互作用和稳定性提供了有价值的见解，进一步证实了其作为治疗剂的潜力。
