Chen Lin, Zheng Qing-Chuan, Zhang Hong-Xing
International Joint Research Laboratory of Nano-Micro Architecture Chemistry, State Key Laboratory of Theoretical and Computational Chemistry, Institute of Theoretical Chemistry, Jilin University, Changchun 130023, P. R. China.
Phys Chem Chem Phys. 2015 Feb 28;17(8):5704-11. doi: 10.1039/c4cp05413j.
A novel, highly conserved chromatin protein, Cren7 is involved in regulating essential cellular processes such as transcription, replication and repair. Although mutations in the DNA-binding loop of Cren7 destabilize the structure and reduce DNA-binding activity, the details are not very clear. Focusing on the specific Cren7-dsDNA complex (PDB code ), we applied molecular dynamics (MD) simulations and the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) free energy calculations to explore the structural and dynamic effects of W26A, L28A, and K53A mutations in comparison to the wild-type protein. The energetic analysis indicated that the intermolecular van der Waals interaction and nonpolar solvation energy play an important role in the binding process of Cren7 and dsDNA. Compared with the wild type Cren7, all the studied mutants W26A, L28A, and K53A have obviously reduced binding free energies with dsDNA in the reduction of the polar and/or nonpolar interactions. These results further elucidated the previous experiments to understand the Cren7-DNA interaction comprehensively. Our work also would provide support for an understanding of the interactions of proteins with nucleic acids.
一种新型的、高度保守的染色质蛋白Cren7参与调控转录、复制和修复等重要细胞过程。尽管Cren7的DNA结合环中的突变会使结构不稳定并降低DNA结合活性，但具体细节尚不清楚。针对特定的Cren7-dsDNA复合物（PDB代码），我们应用分子动力学（MD）模拟和分子力学泊松-玻尔兹曼表面积（MM-PBSA）自由能计算，以探究W26A、L28A和K53A突变相对于野生型蛋白的结构和动力学效应。能量分析表明，分子间范德华相互作用和非极性溶剂化能在Cren7与dsDNA的结合过程中起重要作用。与野生型Cren7相比，所有研究的突变体W26A、L28A和K53A在极性和/或非极性相互作用降低的情况下，与dsDNA的结合自由能均明显降低。这些结果进一步阐明了先前的实验，以全面理解Cren7-DNA相互作用。我们的工作也将为理解蛋白质与核酸的相互作用提供支持。
