CAJ | 학술논문

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.
채용분자동역학모의고찰료이류건대천연태화환원태이도소구상은정성적영향.결과표명:천연태이도소중적이류건한제료기A련화B련적상대운동,유조우은정이도소적주련구상이급이도소활성위점적구상.대우환원태이도소이언,실거이류건사기A련화B련해리,B련적중심라선추우실은,이도치활성위점구상변화.상술분자모의결과여문헌보도적실험결과상부,종분자수평상게시료이류건대우이도소구상은정성적영향궤제,대이도소약물적제제、저존화응용등구유지도의의.
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.