Insights into the effects of mutations on Cren7-DNA binding using molecular dynamics simulations and free energy calculations
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(PD8 code 3LWI),we applied molecular dynamics(MD)simulations and the molecular mechanics Poisson-Soltzmann 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.
Lin Chen Ging-Chuan Zheng Hong-Xing Zhang
International Joint Research laboratory of Nano-Micro Airhitecture Chemistry,State Key Laboratory of International Joint Research laboratory of Nano-Micro Airhitecture Chemistry,State Key Laboratory of
国内会议
大连
英文
471-478
2016-09-24（万方平台首次上网日期，不代表论文的发表时间）