All-atom molecular dynamics simulations reveal significant differences in interaction between antimycin and conserved amino acid residues in bovine and bacterial bc1 complexes.
All-atom molecular dynamics simulations reveal significant differences in interaction between antimycin and conserved amino acid residues in bovine and bacterial bc1 complexes.
复制标题
全原子分子动力学模拟揭示了抗霉素与牛和细菌 bc1 复合物中保守氨基酸残基之间的相互作用存在显着差异。
DOI：
10.1016/j.bpj.2010.12.3705
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发表时间：
2011
影响因子：
3.4
通讯作者：
Shinkarev,VladimirP
中科院分区：
文献类型：
--
作者：
Kokhan,Oleksandr;Shinkarev,VladimirP
抗霉素A是线粒体呼吸链最常用的特异性强效抑制剂。我们使用全原子分子动力学（MD）模拟研究了抗霉素A与嵌入膜中的细菌和牛bc1配合物的Qisite相互作用的动力学方面。MD模拟显示，在Qipocket内，抗霉素具有相当大的构象灵活性和显著的移动性。我们得出结论，在高分辨率x射线结构中观察到的抗霉素结合的许多差异可能是动态的，是由蛋白质和抗霉素在由低激活屏障分隔的能量相似的多个构象状态之间的波动以及抗霉素在Qipocket内的迁移引起的。MD模拟还揭示了牛和细菌中抗霉素与保守氨基酸残基之间的相互作用存在显著差异。抗霉素与保守的Asp-228（牛数量）之间的强氢键在细菌bc1复合体中经常断裂，而在牛bc1复合体中很少断裂。此外，在细菌复合体中，抗霉素与保守的His-201和Lys-227之间的距离始终较大。观察到的差异可能是抗霉素与细菌复合体相互作用较弱的原因。
Antimycin A is the most frequently used specific and powerful inhibitor of the mitochondrial respiratory chain. We used all-atom molecular dynamics (MD) simulations to study the dynamic aspects of the interaction of antimycin A with the Qisite of the bacterial and bovinebc1complexes embedded in a membrane. The MD simulations revealed considerable conformational flexibility of antimycin and significant mobility of antimycin, as a whole, inside the Qipocket. We conclude that many of the differences in antimycin binding observed in high-resolution x-ray structures may have a dynamic origin and result from fluctuations of protein and antimycin between multiple conformational states of similar energy separated by low activation barriers, as well as from the mobility of antimycin within the Qipocket. The MD simulations also revealed a significant difference in interaction between antimycin and conserved amino acid residues in bovine and bacterialbc1complexes. The strong hydrogen bond between antimycin and conserved Asp-228 (bovine numeration) was observed to be frequently broken in the bacterialbc1complex and only rarely in the bovinebc1complex. In addition, the distances between antimycin and conserved His-201 and Lys-227 were consistently larger in the bacterialbc1complex. The observed differences could be responsible for a weaker interaction of antimycin with the bacterialbc1complex.