engleski

Interaction of phosphonium cyanine dyes with DNA

Small molecules targeting DNA/RNA have attracted significant scientific interest due to the medicinal, biochemical and biological implications of such molecular recognition events. Most often these small molecules rely on one dominant non-covalent binding mode for their interaction with double stranded (ds) DNA. The combination of different DNA binding modes of one molecule as well as additional sterical and structural features controlling three-dimensional recognition drew some attention with the aim of developing new more selective drugs or biochemical markers as well as research tools on a molecular level. In this work, the molecular modelling results are presented in combination with spectroscopic measurements for new cyanine dyes in complexes with DNA. This is an example how molecular modelling, particulary the long time molecular dynamics simulation (MD) can be used to rationalize the experimental results on molecular interactions. The molecular modelling was performed with AMBER10 suite. AMBER ff99SB and GAFF force field were used to parametrize molecules. During 23.6 ns of MD simulations at both room and elevated temperature the cyanine compounds reoriented, but have not left the DNA minor groove in which they were initially positioned, whereby two possible orientations of monomer molecule showed to be equally possible. Moreover, at different dye/DNA ratio molecular modelling results proved posibility of dye dimmer formation within DNA minor groove. Thus, the obtained computational results rationalized the experimentally determined affinity of cyanine dyes towards DNA.

phosphonium cyanine dyes; DNA; non-covalent binding mode; molecular modelling; spectroscopy; AMBER10; AMBER ff99SB and GAFF force filed

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