Structural Bioinformatics Lab, CSIR-Institute of Himalayan Bioresource Technology (CSIR-IHBT), Palampur, HP 176061, India; Biotechnology division, CSIR-IHBT, Palampur, HP 176061, India; Academy of Scientific & Innovative Research (AcSIR), Ghaziabad-201002, India.
Structural Bioinformatics Lab, CSIR-Institute of Himalayan Bioresource Technology (CSIR-IHBT), Palampur, HP 176061, India; Biotechnology division, CSIR-IHBT, Palampur, HP 176061, India; Academy of Scientific & Innovative Research (AcSIR), Ghaziabad-201002, India.
Carbohydr Polym. 2023 Nov 1;319:121162. doi: 10.1016/j.carbpol.2023.121162. Epub 2023 Jul 1.
The study of inclusion complexes of Chrysin (ChR) with three forms of cyclodextrins (CDs) α-, β-, and γ-CD was accomplished to examine the stability of ChR inside the central cavities of CDs. The aim of study was to identify the most suitable form of CD to improve the hydro-solubility of poorly soluble ChR bioactive molecule. Microsecond timescale molecular dynamics (MD) simulations were performed on four inclusion complexes (α-CD/ChR, β-CD/ChR, and two conformations of γ-CD/ChR) to examine the dynamics of ChR inside the cavity of CDs. The first conformation of γ-CD/ChR inclusion complex (γ-CD1/ChR) was identified to possess the highest affinity between host and guest molecule on the basis of binding energy calculated by employing Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) and umbrella sampling simulations. To further strengthen the claims of classical and biased MD studies, Our own N-layered Integrated molecular Orbital and Molecular mechanics (ONIOM) (wB97XD/6-311+g(d,p):pm7) calculations were performed on the selected inclusion complexes. The ONIOM based complexation energy reaffirmed that ChR had highest affinity for the γ-CD1 host molecule. Further, the non-covalent interaction analysis was conducted using Multiwfn software on QM-optimized inclusion complexes with wB97XD/6-311+G(d,p) model chemistry, revealing non-covalent interactions between ChR and CDs. This atomic level information helped us to gain better insights into critical atoms of ChR and CD that participated in intermolecular interactions and identify γ-CD as a suitable host molecule for improving the hydro-solubulity of ChR. The structural insights would help to derive new derivatives of γ-CD with better host capacity.
将白杨素（ChR）与三种形式的环糊精（CDs）α-、β-和 γ-CD 形成包合物的研究旨在考察 ChR 在 CDs 中心腔体内的稳定性。研究目的是确定最适合的 CD 形式，以提高难溶性 ChR 生物活性分子的水溶解度。对四个包含复合物（α-CD/ChR、β-CD/ChR 和两种 γ-CD/ChR 构象）进行微秒时间尺度的分子动力学（MD）模拟，以考察 ChR 在 CDs 腔体内的动力学。基于通过分子力学泊松-玻尔兹曼表面面积（MM-PBSA）和伞状采样模拟计算的结合能，确定 γ-CD1/ChR 包含复合物（γ-CD1/ChR）具有最高的主体和客体分子之间的亲和力。为了进一步加强经典和有偏 MD 研究的结论，我们对选定的包含复合物进行了自己的 N 层综合分子轨道和分子力学（ONIOM）（wB97XD/6-311+g(d,p):pm7）计算。基于 ONIOM 的络合能再次证实，ChR 与 γ-CD1 主体分子具有最高的亲和力。此外，使用 Multiwfn 软件对 QM 优化的包含复合物进行非共价相互作用分析，采用 wB97XD/6-311+G(d,p)模型化学，揭示了 ChR 与 CDs 之间的非共价相互作用。这些原子水平的信息帮助我们更好地了解参与分子间相互作用的 ChR 和 CD 的关键原子，并确定 γ-CD 是提高 ChR 水溶解度的合适主体分子。结构见解将有助于得出具有更好主体容量的新型 γ-CD 衍生物。
