Mapping the morphological identifiers of distinct conformations via the protein translocation current in nanopores.
Mapping the morphological identifiers of distinct conformations via the protein translocation current in nanopores.
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DOI：
10.1039/d0nr07413f
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发表时间：
2021-03
期刊：
影响因子：
6.7
通讯作者：
Mingkun Zhang;Shenbao Chen;Jinrong Hu;Qihan Ding;Linda Li;Shouqin Lü;M. Long
中科院分区：
文献类型：
--
作者：
Mingkun Zhang;Shenbao Chen;Jinrong Hu;Qihan Ding;Linda Li;Shouqin Lü;M. Long
蛋白质的构象变化在实现其功能和揭示各种生物学过程中的潜在机制方面起着至关重要的作用。在纳米孔技术中，利用电流-电阻脉冲的时间指纹来监测蛋白质构象仍然具有挑战性。在这里，一个典型的整合素，αxβ2，不同的构象的低分辨率形态估计通过相对封锁电流从全原子分子动力学（MD）模拟。αxβ2的不同构象状态可以直接用体积和形状标识符来解释。从蛋白质封闭的纳米孔内的电导率分布分析离子电流中的蛋白质调制。将离散模型与球体近似相结合，开发了一种基于MD的方法，以理论上预测用于感测αxβ2的纳米孔的体积和形状。该方法也适用于指定其他六种蛋白质的形态标识符，理论预测与实验测量结果吻合良好。这些结果增强了该方法用于纳米孔中蛋白质构象鉴定的有效性。
Conformational changes of proteins play a vital role in implementing their functions and revealing the underlying mechanisms in various biological processes. It is still challenging to monitor protein conformations with temporal fingerprints of current-resistance pulses in the nanopore technique. Here the low-resolution morphologies of different conformations of a typical integrin, αxβ2, were estimated via relative blockade currents simulated from all-atom molecular dynamics (MD). Distinct conformational states of αxβ2 were directly explained by the volume and shape identifiers. Protein modulation in ionic current was analyzed from the conductivity distribution inside the protein-blocked nanopore. Combining a discrete model with spheroidal approximation, a MD-based approach was developed to theoretically predict the volume and shape of the nanopore for sensing αxβ2. This method was also applicable in specifying morphological identifiers of six other proteins, and the theoretical predictions are in good agreement with the experimental measurements. These results potentiated the validity of this method for the conformational identification of proteins in nanopores.