a School of Chemical and Biotechnology , SASTRA University , Thanjavur 613401 , India.
J Biomol Struct Dyn. 2017 Dec;35(16):3540-3554. doi: 10.1080/07391102.2016.1261741. Epub 2016 Dec 9.
Sequence-specific binding of proteins to DNA is essential for almost all the cellular processes like transcription, translation, replication, etc. One among the various mechanisms that has been identified so far that contributes to the specificity in protein-DNA interaction is the DNA conformational change. Electrostatic neutralization of the phosphate groups by the positively charged amino acid residues in proteins is thought to bring about such conformational changes in DNA. Here, we employ molecular dynamics simulations to examine the effect of charge on amino acids Lys113, Arg145, and Asp91 which are attached to the scissile phosphate on the conformation of DNA in EcoRI-DNA complex. The results indicate that the charge of these amino acids is essential for maintaining the local conformation of DNA in the EcoRI-bound form. Interestingly, we observe that the positively charged amino acids Lys113 and Arg145 have a long-range influence on the DNA conformation, whereas the negatively charged amino acid Asp91 has only a localized effect on the DNA conformation. The charge on the amino acids also alters the collective dynamics of EcoRI. Collectively, the results shed light on the diversity of the effect of charges on DNA conformation as well as on protein dynamics.
蛋白质与 DNA 的序列特异性结合对于几乎所有的细胞过程都是至关重要的，如转录、翻译、复制等。迄今为止，已经确定了多种有助于蛋白质-DNA 相互作用特异性的机制，其中之一是 DNA 的构象变化。蛋白质中带正电荷的氨基酸残基静电中和磷酸基团，被认为会导致 DNA 发生这种构象变化。在这里，我们采用分子动力学模拟来研究与裂解磷酸基相连的氨基酸残基 Lys113、Arg145 和 Asp91 的电荷对 EcoRI-DNA 复合物中 DNA 构象的影响。结果表明，这些氨基酸的电荷对于维持 EcoRI 结合形式下 DNA 的局部构象是必不可少的。有趣的是，我们观察到带正电荷的氨基酸 Lys113 和 Arg145 对 DNA 构象有远程影响，而带负电荷的氨基酸 Asp91 对 DNA 构象只有局部影响。氨基酸上的电荷也改变了 EcoRI 的集体动力学。总的来说，这些结果揭示了电荷对 DNA 构象以及蛋白质动力学的影响的多样性。
