Conformation-dependent DNA attraction.
Understanding how DNA molecules interact with other biomolecules is related to how they utilize their functions and is therefore critical for understanding their structure-function relationships. For a long time, the existence of Z-form DNA (a left-handed double helical version of DNA, instead of the common right-handed B-form) has puzzled the scientists, and the definitive biological significance of Z-DNA has not yet been clarified. In this study, the effects of DNA conformation in DNA-DNA interactions are explored by molecular dynamics simulations. Using umbrella sampling, we find that for both B- and Z-form DNA, surrounding Mg(2+) ions always exert themselves to screen the Coulomb repulsion between DNA phosphates, resulting in very weak attractive force. On the contrary, a tight and stable bound state is discovered for Z-DNA in the presence of Mg(2+) or Na(+), benefiting from their hydrophobic nature. Based on the contact surface and a dewetting process analysis, a two-stage binding process of Z-DNA is outlined: two Z-DNA first attract each other through charge screening and Mg(2+) bridges to phosphate groups in the same way as that of B-DNA, after which hydrophobic contacts of the deoxyribose groups are formed via a dewetting effect, resulting in stable attraction between two Z-DNA molecules. The highlighted hydrophobic nature of Z-DNA interaction from the current study may help to understand the biological functions of Z-DNA in gene transcription.
Institute of Quantitative Biology and Medicine, School for Radiological & Interdisciplinary Sciences (RAD-X), Soochow University, Suzhou, China 215123.
Weifeng
W
Li
Lars
L
Nordenskiöld
Ruhong
R
Zhou
Yuguang
Y
Mu
D001665:Binding Sites; D003198:Computer Simulation; D059371:DNA, B-Form / Q000737:chemistry* / Q000648:ultrastructure*; D043542:DNA, Z-Form / Q000737:chemistry* / Q000648:ultrastructure*; D008274:Magnesium / Q000737:chemistry*; D008956:Models, Chemical; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation; D055672:Static Electricity; D013314:Stress, Mechanical
D059371:DNA, B-Form; D043542:DNA, Z-Form; D008274:Magnesium