光谱学结合分子动力学研究秋水仙碱与血红蛋白之间相互作用机制

Study of interaction between colchicine and hemoglobin by spectra analysis and computational simulation methods

本文通过分子光谱、分子对接以及分子动力学模拟等技术手段探究了秋水仙碱与血红蛋白(Hb)之间相互作用的模式与机制。分子光谱和非辐射能量转移理论研究结果表明秋水仙碱通过范德华力与Hb结合,并导致Hb的构象发生改变。分子对接和分子动力学研究发现秋水仙碱在Hb的中央空腔与其形成稳定的复合物,并导致Hb的结构变得紧密,从而驱动Hb二级结构中的α-螺旋、β-转角、弯曲、无规则卷曲等结构的含量发生显著变化。Hb的某些氨基酸残基如:Trp37(β2)、Ala130(α2)、Pro90(α1)、Thr137(α1)、Tyr35(β2)等在它们结合的过程中发挥着至关重要的作用。实验数据和模拟研究结果相互印证,为进一步揭示秋水仙碱在生物体内的作用机制提供重要信息和参考依据。

The interaction mechanisms between colchicine and hemoglobin were investigated by a combination of multi-spectroscopy,molecular docking and molecular dynamics simulation.The results of spectroscopy analyses and non-radiation energy transfer theory revealed that the stable complex of colchicine-hemoglobin was formed,and van der Waals forces played a dominant role in this system.It is also showed that the conformational structure of hemoglobin was changed as the result of this reaction.Molecular docking indicated that the primary binding site for colchicine was located in the center cavity of hemoglobin.Molecular dynamics simulation suggested that the content ofα-helix,bend,turn,and coil of hemoglobin was Significant changed,and some Amino acid residues such as Trp37(β2),Ala130(α2),Pro90(α1),Thr137(α1),and Tyr35(β2)played major role in the binding reaction.The results of present study would provide reliable information for the effect of colchicine on organism.