engleski

Molecular modelling of phosphonium cyanine dyes in complex with DNA

Huge number of medicinal, biochemical and biological implications of DNA/RNA targeting small molecules resulted in enormous scientific interest in them. 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. The molecular modelling results are compared with spectroscopic measurements for new cyanine dyes in complexes with DNA. This is an example how molecular modelling, particularly 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 parameterize 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. According to the calculated binding free energies the both orientations are similarly possible. Moreover, at different dye/DNA ratio molecular modelling results proved possibility of dye dimmer formation within DNA minor groove. Thus, the obtained computational results rationalized the experimentally determined affinity of cyanine dyes towards DNA.

molecular modelling; double stranded DNA; cyanine dyes; AMBER10; GAFF; ff99sb; spectroscopic measurements

nije evidentirano