Defective structures,such as DNA mismatches,occur in DNA with a high frequency in some biological processes.They are difficult to identify and have recently become the focus of singlemolecule investigations.Three sing...Defective structures,such as DNA mismatches,occur in DNA with a high frequency in some biological processes.They are difficult to identify and have recently become the focus of singlemolecule investigations.Three single-molecule experiments were successively conducted to detect the effects of DNA mismatch on the stability of DNA hairpins.However,there was no consensus regarding the results of the intermediate state caused by DNA mismatch.Based on the extended ox-DNA model,DNA mismatch was introduced to the stem of DNA hairpins with different stem lengths(12-20 bps)and 4T in hairpin loops.The intermediate state and its dependence on the position of the DNA mismatch in the stem from the hairpin loop were systematically studied.The results indicated that DNA mismatch definitely reduced the critical forces of DNA hairpins.At the same time,a common rule about the dependence of the intermediate state on the position of DNA mismatch was generalized in a phase diagram constructed in a phase space of a scaled position of DNA mismatch.Three segments on its diagonal line corresponded to the ranges of the scaled position of DNA mismatch[0,0.55),[0.55,0.85),and[0.85,1],respectively.In the[0.55,0.85)range,the extension probability distribution of DNA hairpins had unfolded,intermediate,and folded states.In contrast,in the other ranges[0,0.55)and[0.85,1],the extension probability distributions had unfolded and folded states.The scaled positions of DNA mismatch for the DNA hairpins used in the three single-molecule experiments(0.65,0.4736,and 0.5)fell in the ranges[0.55,0.85)and[0,0.55).Obviously,the common rule generalized in the phase diagram not only clarifies the nonconsensus between the three single-molecule experiments but also highlights the design of single-molecule experiments in the future.展开更多
基金The National Natural Science Foundation of China under Grant Nos.11864006,11874309,12164007,and 12204118Guizhou Scientific and Technological Program(20185781,ZK(2021)004,ZK(2021)032 and20185781-15)Guizhou Provincial Graduate Scientific Research Foundation(YJSKYJJ(2021)066)
文摘Defective structures,such as DNA mismatches,occur in DNA with a high frequency in some biological processes.They are difficult to identify and have recently become the focus of singlemolecule investigations.Three single-molecule experiments were successively conducted to detect the effects of DNA mismatch on the stability of DNA hairpins.However,there was no consensus regarding the results of the intermediate state caused by DNA mismatch.Based on the extended ox-DNA model,DNA mismatch was introduced to the stem of DNA hairpins with different stem lengths(12-20 bps)and 4T in hairpin loops.The intermediate state and its dependence on the position of the DNA mismatch in the stem from the hairpin loop were systematically studied.The results indicated that DNA mismatch definitely reduced the critical forces of DNA hairpins.At the same time,a common rule about the dependence of the intermediate state on the position of DNA mismatch was generalized in a phase diagram constructed in a phase space of a scaled position of DNA mismatch.Three segments on its diagonal line corresponded to the ranges of the scaled position of DNA mismatch[0,0.55),[0.55,0.85),and[0.85,1],respectively.In the[0.55,0.85)range,the extension probability distribution of DNA hairpins had unfolded,intermediate,and folded states.In contrast,in the other ranges[0,0.55)and[0.85,1],the extension probability distributions had unfolded and folded states.The scaled positions of DNA mismatch for the DNA hairpins used in the three single-molecule experiments(0.65,0.4736,and 0.5)fell in the ranges[0.55,0.85)and[0,0.55).Obviously,the common rule generalized in the phase diagram not only clarifies the nonconsensus between the three single-molecule experiments but also highlights the design of single-molecule experiments in the future.
