Molecular Dynamics Simulation Studies Of The Interactions Between Carbon-based Nanomaterials And Nucleic Acid

Carbon-based nanomaterials are widely used in biomedical fields due to their unique photothermal and catalytic properties.However,their toxic effects on living organisms cannot be ignored.At the molecular level,carbon-based nanomaterials are easily adsorbed by biomacromolecules(such as proteins,nucleic acid molecules,etc.),which may lead to severe distortion of the structure of biomacromolecules and loss of their original biological functions.Experiments have shown that carbon-based nanomaterials can directly interact with DNA and have toxic effects,such as causing oxidative damage,double-strand breaks,structural distortion of DNA,and inhibition of biological processes such as replication and transcription.This toxicity may be related to the physical properties of carbon-based nanomaterials(such as size,shape,surface modification,etc.)and the structure and environment of DNA molecules.Therefore,studying the rules and toxicity mechanisms of the interaction between carbon-based nanomaterials and DNA can help find methods to reduce their toxicity and promote their wide application in the biomedical field.In this paper,we explored the relationship between the size of nanomaterials and toxicity,and analyzed the binding behavior and effects of sub-nanometersized C28 molecules on double-stranded DNA.In addition,we further investigated the structural effects of carbon-based nanomaterials on non-standard Z-base DNA.The Z base(2,6Diaminopurine)exists in the genome of cyanophage S-2L,completely replacing adenine(A)and forming three hydrogen bonds with thymine(T).Recently,the discovery of the biosynthetic pathway of Z-base in cyanophage has stimulated research interest in this non-standard DNA.In this thesis,the paper was carried out based on molecular dynamics simulations,with the following main research contents:1.We systematically investigated the binding behavior of sub-nanometer-sized C28 molecules to double-stranded DNA and their effects on DNA.Our study shows that C28 molecules can tightly bind to the ends or minor grooves of nucleic acids and affect the width of the minor groove.Compared to other nanomaterials such as carbon nanotubes,graphene,and fullerenes,C28 molecules do not cause significant structural distortion when binding to DNA and have less impact on DNA dynamics,demonstrating higher biocompatibility.In addition,we found that C28 molecules have a significant sequence preference in binding,favoring regions with high GC content because the minor grooves in these regions are usually wider than those in AT-rich regions.The binding properties of C28 molecules have great potential for their applications in the field of biomedicine.Furthermore,due to the tendency of C28 molecules to aggregate in regions rich in GC base pairs,they may also help develop detection methods targeting specific DNA sequences.2.We analyzed and compared the conformational features of Z-base containing DNA and normal DNA and investigate the effects of fullerene(C60)and graphene on the structures of DNA containing Z-base and normal DNA.The results showed that C60 molecules can bind to both types of DNA and form stable complexes.During the simulation process,the hydrogen bonds of normal DNA were broken and the double helix structure was disrupted,while C60 did not cause significant structural damage to DNA containing Z-base,exhibiting better biocompatibility.Through PCA analysis and conformational entropy calculation,we found that DNA containing Z-base exhibited more stable dynamic properties,indicating its greater rigidity.Similar to the results of C60,graphene had a stronger binding affinity with normal DNA,resulting in severe disruption of the hydrogen bonds and double helix structure between the base pairs.The difference in nanotoxicity of carbon-based nanomaterials on the two types of DNA may originate from the stronger interactions between the double helix of DNA containing Z-base,making the overall structure of DNA more stable.This stability may also be related to the additional amino groups in DNA containing Z-base and the stacking interactions of adjacent base pairs,which warrants further experimental exploration.Based on the above research results,we hope that these studies can promote and guide the biomedical applications of carbon-based nanomaterials and the future research of Z-base DNA.The toxicity of nanomaterials is highly correlated with their size,and C28 with sub-nanometer size has higher biocompatibility.Z-base DNA has higher structural stability,and carbon-based nanomaterials have lower nanotoxicity to it than to normal DNA.This may help people better understand the mechanism of nanomaterials in biological systems and provide theoretical reference for the research of nanomedicine and biomedical applications.