Abstract:

Molecular dynamics simulation of the impact of disulfide bond on the conformational stability of native and reduced insulin was conducted at all-atom level.It was shown that disulfide bond restricted the relative motion of chain A and chain B in native insulin and thus strengthened the conformational stability for both the domain and active site.For reduced insulin without the native disulfide bonds，the conformation of the activate site altered while chain A and chain B dissociated.Moreover，the simulation suggested that the central helix in chain B would be unstable after disengaging the disulfide bonds，i.e.，the deactivation was irreversible.The above described simulation reproduced the experimental observations reported in the literatures，and established a molecular insight into the impact of disulfide bonds on the conformational stability of insulin，and would be of fundamental importance to the processing，formulating and pharmaceutical application of insulin.

Key words:

胰岛素, 二硫键, 分子动力学模拟

摘要：

采用分子动力学模拟考察了二硫键对天然态和还原态胰岛素构象稳定性的影响。结果表明：天然态胰岛素中的二硫键限制了其A链和B链的相对运动，有助于稳定胰岛素的主链构象以及胰岛素活性位点的构象。对于还原态胰岛素而言，失去二硫键使其A链和B链解离，B链的中心螺旋趋于失稳，而导致活性位点构象变化。上述分子模拟结果与文献报道的实验结果相符，从分子水平上揭示了二硫键对于胰岛素构象稳定性的影响机制，对胰岛素药物的制剂、储存和应用等具有指导意义。

关键词:

胰岛素, 二硫键, 分子动力学模拟