文献类型：期刊文献

英文题名：Sulfur-substitution-induced base flipping in the DNA duplex

作者：Sun, Zhaoxi[1,2];Wang, Xiaohui[1,3];Zhang, John Z. H.[1,4,5];He, Qiaole[6,7]

机构：[1]East China Normal Univ, Sch Chem & Mol Engn, State Key Lab Precis Spect, Shanghai 200062, Peoples R China;[2]Forschungszentrum Julich, Computat Biomed IAS 5 INM 9, D-52425 Julich, Germany;[3]USI, Inst Computat Sci, Via Giuseppe Buffi 13, CH-6900 Lugano, Ticino, Switzerland;[4]NYU Shanghai, NYU ECNU Ctr Computat Chem, Shanghai 200062, Peoples R China;[5]NYU, Dept Chem, New York, NY 10003 USA;[6]Forschungszentrum Julich, IBG 1 Biotechnol, Wilhelm Johnen Str 1, D-52425 Julich, Germany;[7]East China Univ Sci & Technol, R&D Ctr Separat & Extract Technol Fermentat Ind, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China

年份：2019

卷号：21

期号：27

起止页码：14923

外文期刊名：PHYSICAL CHEMISTRY CHEMICAL PHYSICS

收录：;EI(收录号：20201708549203);WOS:【SCI-EXPANDED(收录号:WOS:000477969700048)】；

基金：This work was supported the China Scholarship Council. Computer access to the CLAIX cluster of RWTH Aachen University and clusters of Forschungszentrum Juelich is gratefully acknowledged. We thank Prof. Dr Paolo Carloni (Forschungszentrum Juelich) and the anonymous reviewers for valuable comments and critical reading.

语种：英文

外文关键词：Gene encoding - Thermodynamic stability - Amber

摘要：Base flipping is widely observed in a number of important biological processes. The genetic codes deposited inside the DNA duplex become accessible to external agents upon base flipping. The sulfur substitution of guanine leads to thioguanine, which alters the thermodynamic stability of the GC base pairs and the GT mismatches. Experimental studies conclude that the sulfur substitution decreases the lifetime of the GC base pair. In this work, under three AMBER force fields for nucleotide systems, we firstly performed equilibrium and nonequilibrium free energy simulations to investigate the variation of the thermodynamic profiles in base flipping upon sulfur substitution. It is found that the bsc0 modification, the bsc1 modification and the OL15 modification of AMBER force fields are able to qualitatively describe the sulfur-substitution dependent behavior of the thermodynamics. However, only the two last-generation AMBER force fields are able to provide quantitatively correct predictions. The second computational study on the sulfur substitutions focused on the relative stability of the S6G-C base pair and the S6G-T mismatch. Two conflicting experimental observations were reported by the same authors. One suggested that the S6G-C base pair was more stable, while the other concludes that the S6G-T mismatch was more stable. We answered this question by constructing the free energy profiles along the base flipping pathway computationally.