Nejvíce citovaný článek - PubMed ID 26194779
Multiscale modelling of DNA mechanics
Nucleic acid double helices in their DNA, RNA, and DNA-RNA hybrid form play a fundamental role in biology and are main building blocks of artificial nanostructures, but how their properties depend on temperature remains poorly understood. Here, we report thermal dependence of dynamic bending persistence length, twist rigidity, stretch modulus, and twist-stretch coupling for DNA, RNA, and hybrid duplexes between 7°C and 47°C. The results are based on all-atom molecular dynamics simulations using different force field parameterizations. We first demonstrate that unrestrained molecular dynamics can reproduce experimentally known mechanical properties of the duplexes at room temperature. Beyond experimentally known features, we also infer the twist rigidity and twist-stretch coupling of the hybrid duplex. As for the temperature dependence, we found that increasing temperature softens all the duplexes with respect to bending, twisting, and stretching. The relative decrease of the stretch moduli is 0.003-0.004/°C, similar for all the duplex variants despite their very different stretching stiffness, whereas RNA twist stiffness decreases by 0.003/°C, and smaller values are found for the other elastic moduli. The twist-stretch couplings are nearly unaffected by temperature. The stretching, bending, and twisting stiffness all include an important entropic component. Relation of our results to the two-state model of DNA flexibility is discussed. Our work provides temperature-dependent elasticity of nucleic acid duplexes at the microsecond scale relevant for initial stages of protein binding.
We present a systematic study of the long-timescale dynamics of the Drew-Dickerson dodecamer (DDD: d(CGCGAATTGCGC)2) a prototypical B-DNA duplex. Using our newly parameterized PARMBSC1 force field, we describe the conformational landscape of DDD in a variety of ionic environments from minimal salt to 2 M Na(+)Cl(-) or K(+)Cl(-) The sensitivity of the simulations to the use of different solvent and ion models is analyzed in detail using multi-microsecond simulations. Finally, an extended (10 μs) simulation is used to characterize slow and infrequent conformational changes in DDD, leading to the identification of previously uncharacterized conformational states of this duplex which can explain biologically relevant conformational transitions. With a total of more than 43 μs of unrestrained molecular dynamics simulation, this study is the most extensive investigation of the dynamics of the most prototypical DNA duplex.
- MeSH
- B-DNA chemie ultrastruktura MeSH
- chlorid draselný chemie MeSH
- chlorid sodný chemie MeSH
- konformace nukleové kyseliny * MeSH
- molekulární modely MeSH
- simulace molekulární dynamiky * MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- B-DNA MeSH
- chlorid draselný MeSH
- chlorid sodný MeSH
