| dc.description.abstract | Biomolecules are composed mainly of six major chemical elements: carbon, hydrogen, nitrogen, oxygen, phosphorus, and sulfur. Recent studies have suggested the possibility of sustaining life if the phosphorus is substituted by arsenic. Although this issue is still controversial, it is interest to investigate the properties of arsenated-lipid bilayers and arsenated-DNA to evaluate the possibility.
In the first part, we simulated arsenated-lipid, 1-palmitoyl-2-oleoyl-sn-glycero-3- arsenocholine (POAC), lipid bilayers using all-atom molecular dynamics to understand basic structural and dynamical properties, in particular, the differences from analogous 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, (POPC) lipid bilayers. Our simulations showed that POAC lipid bilayers have distinct structural and dynamical properties from those of native POPC lipid bilayers. Relative to POPC lipid bilayers, POAC lipid bilayers have a more compact structure with smaller lateral areas and greater order. The compact structure of POAC lipid bilayers is due to the fact that more inter-lipid salt bridges are formed with arsenate-choline compared to the phosphate-choline of POPC lipid bilayers. These inter-lipid salt bridges bind POAC lipids together and also slow down the head group rotation and lateral diffusion of POAC lipids. Thus, it would be anticipated that POAC and POPC lipid bilayers would have different biological implications.
In the second part, we study the double-stranded native and As-substituted DNA with five base pairs using density functional theory to investigate the impacts on the conformational and electronic properties upon arsenic/phosphorus interchange. The Minnesota density functional M06-2X well reproduces of the experimental structure of native DNA; while the commonly used B3LYP functional yields large deviation. The optimized structure of native DNA at M06-2X/6-31G(d,p) level is BI-form conformation, which is consistent with the experimental result. Interestingly, the optimized structure of As-DNA at M06-2X/6-31G(d,p) level also remains a BI-form conformation. The structures of native and arsenated-DNA share some common structural features; nevertheless, they have some differences such as hydrophobic core, DNA groove, and helix twist. More interestingly, the As-DNA has stronger molar absorbance than native DNA suggested that As-DNA might be damaged quickly than native DNA under UV radiation. | en_US |