从晶体结构出发,应用分子对接和结合自由能分析,研究了唾液酸转移酶(Sialyltransferase, ST)与其抑制剂大豆皂苷Ⅰ的相互作用机理,确定了它们的作用位点、作用力类型及大小。结果表明:范德华力和静电相互作用是复合物形成的主要驱动力,极性溶剂化能则起相反作用；8个氨基酸残基Gly149、Ser151、Met172、Asn173、Phe292、Trp300、His301、Ser325与大豆皂苷Ⅰ形成疏水相互作用,11个氨基酸残基Asn150、Tyr194、Ser271、Thr272、Gly273、Ile274、Gly291、Gly293、His302、Glu305、Glu324与大豆皂苷Ⅰ形成氢键作用；大豆皂苷Ⅰ占据了ST与底物胞苷一磷酸-β-N-乙酰神经氨酸相互作用的12个氨基酸残基中的11个,可起到竞争性抑制的作用。
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The molecular mechanism for the binding sites, driving forces and the interaction intensity between sialyltransferase (ST) and soyasaponin I was investigated by molecular docking and free energy calculation based on the crystal structure. The van der Waals force and electrostatic interaction were considered as the main driving forces, while polar solvation energy behaved in an opposite manner. The hydrophobic interaction was formed between soyasaponin I and eight amino acid residues, i.e., Gly149, Ser151, Met172, Asn173, Phe292, Trp300, His301, and Ser325. Hydrogen bonding was found between soyasaponin I and eleven amino acid residues, including Asn150, Tyr194, Ser271, Thr272, Gly273, Ile274, Gly291, Gly293, His302, Glu305, and Glu324. Soyasaponin I was a competitive inhibitor which occupied 11 of the 12 amino acid residues that accommodated the substrate CMP-β-N-acetylneuramic acid. These results provide a theoretical basis for the development and utilization of soyasaponin I as a ST inhibitor.
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