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Abstract：
Polygonatum sibiricum (P. sibiricum), recognized as a precious nourishing Chinese traditional medicine, exhibits the pharmacological effect of anti-aging. In this work, we proposed a novel mechanism underlying this effect related to the less studied bioactive compounds fructooligosaccharides in P. sibiricum (PFOS) to identify the inhibition effect of the small glycosyl molecules on the age-related zinc metalloprotease carbonic anhydrase II (CA II). Molecular docking and molecular dynamics simulation were used to investigate the structural and energetic properties of the complex systems consisting of the CA II enzyme and two possible structures of PFOS molecules (PFOS-A and PFOS-B). The binding affinity of PFOS-A (-7.27 ± 1.02 kcal/mol) and PFOS-B (-8.09 ± 1.75 kcal/mol) shows the spontaneity of the binding process and the stability of the combination in the solvent. Based on the residue energy decomposition and nonbonded interactions analysis, the C-, D- and G-sheet fragments of the CA II were found to be crucial in binding process. Van der Waals interactions form on the hydrophobic surface of CAII mainly with 131PHE and 135VAL, while hydrogen bonds form on the hydrophilic surface mainly with 67ASN and 92GLN. The binding of PFOS results in the blocking of the zinc ions pocket and then inhibiting its catalytic activity, the stability of which has been further demonstrated by free energy landscape. These findings provide evidence of the effective inhibition of PFOS to CA II enzyme, which leads to a novel direction for exploring the mechanism of traditional Chinese medicine focused on small molecule fructooligosaccharides.
摘要：
黄精（P.sibiricum),被公认为珍贵的滋养中药，表现出抗衰老的药理作用。在这项工作中,我们提出了一种新的机制，该机制与研究较少的生物活性化合物sybiricum（PFOS）相关，以确定小糖基分子对年龄相关的锌金属蛋白酶碳酸酐酶II（CAII）的抑制作用。使用分子对接和分子动力学模拟来研究由CAII酶和PFOS分子的两种可能结构（PFOS-A和PFOS-B）组成的复杂系统的结构和能量性质。PFOS-A（-7.27±1.02kcal/mol）和PFOS-B（-8.09±1.75kcal/mol）的结合亲和力显示了结合过程的自发性和组合在溶剂中的稳定性。基于剩余能量分解和非键合相互作用分析，C-，发现CAII的D-和G-片片段在结合过程中至关重要。范德华相互作用主要与131PHE和135VAL在CAII疏水表面形成,而亲水表面主要与67ASN和92GLN形成氢键。全氟辛烷磺酸的结合导致锌离子口袋的阻断，然后抑制其催化活性，自由能景观进一步证明了其稳定性。这些发现提供了全氟辛烷磺酸对CAII酶有效抑制的证据，为中药小分子低聚果糖的作用机制探索开辟了新的方向。
