Effect Of Interaction Between Loop Bases And Ions On Stability Of G-quadruplex DNA

DNA is regarded as the carrier of genetic information and is an essential biological macromolecule in biological growth and development.There is a special g-quadruple DNA which directly participates in the regulation of genetic information in the telomere and transcription promoter region.Due to its important biological functions and its important potential in medical field,people have been very keen on the structure and function of g-tetrahedron.G-tetrahedron is a high-level structure formed by folding DNA or RNA,and its basic unit is G-tetrad.G-tetrahedron is the main body of g-tetrahedron formed by 4 guanine connected by hydrogen bond and two circular plane structures,while two or more g-tetramers are formed by ? ? accumulation and the combination of cation ions.The loop region of g-tetra-chain is called the loop region of g-tetra-chain,which consists of adenine(a)and thymine(T)bases at both ends of the main body.According to the different structure,the loop base chain can be divided into cross chain structure and side chain structure.The results show that g-tetrahedron usually needs to interact with metal cations to stabilize its structure,such as na+ often appears in the plane space of g-tetrahedron,while k+is mostly located between two g-tetrahedrons to help g-tetrahedron stabilize the structure.Then we find that the dynamic behavior of ring structure has a great influence on the adjacent g-tetrahedron,which affects the stability of the whole g-tetrahedron.Moreover,from the experimental results,it is difficult to understand the influence of ring structure on the structure and stability of g-tetrahedron from the sequence,length and position of the ring structure separately.The sequence,length and position of the ring structure are mixed together.Moreover,it is not that other single strand DNA has a large structural fluctuation,but has certain structure.All of these need us to understand the influence of ring structure on the structure and stability of g-tetra-chain Further from the molecular level to explore,find out the physical mechanism behind it.What we have to do is to explore the interaction between metal ions and the base groups in loop region from the perspective of all atoms,and its influence on the structure and stability of g-tetrahedron.Considering that the metal ions are close to the surface of g-tetrahedral DNA,the charge rearrangement and the long distance transfer of charge when the base is stacked,we use quantitative calculation and all atom molecular dynamics simulation under the polarization force field.First,we choose the monovalent ions na+,K+The effects of different sequences of loop on the stability of g-tetrachain were studied.Then we used mg2+,ca2+ containing high valence ions to investigate the influence of different ions on the stability of loop region and g-quadruple.Finally,we studied the influence of ions on the stability of loop region of different structures and the internal relationship between loop structure stability and g-tetrahedral backbone stability.The research in this work not only helps people understand the structure and stability mechanism of g-tetra-strand DNA,but also provides new clues and ideas for people to design effective g-tetra-chain structure stabilizer for the treatment of various genetic diseases.