engleski

Molecular modelling of bisphenanthridinium- nucleobase conjugates

Molecular modelling results are presented in combination with the spectroscopic measurements for a series of nucleobase conjugates of bisphenanthridinium as well as their non- covalent complexes with UMP and AMP. AMBER ff03 and GAFF force fields were used to parametrize molecules and Molecular Dynamics (MD) simulations were accomplished with the program AMBER9. The simulations were performed in explicit water (TIP3P water type) using periodic boundary conditions. During the MD simulations conformation of the molecules relaxed ; however majority of molecules remained in their folded, more or less stacked conformation with no water molecules accommodated within the two phenanthridinium rings. The initial structure of the complex between S21 and UMP was built in a way to enable adenine from S21 and uracil from UMP to form the Watson-Crick type of H-bonds. These H- bonds were preserved during the geometry optimization. However, during the MD simulation the conformation of the complex changed and stabilized in a conformation with adenine in the stacking interaction with one phenanthridinium ring, and uracil with the other. In this interaction the hydrophobic pocket made by two phenanthridinium rings and the alkyl linker is very functional since there is no water molecule within it to compete with uracil from UMP for the hydrogen bond. This result is in accord with the spectroscopic measurements and the high binding affinity of S21 toward UMP .

bisphenanthridinium-nucleobase conjugates; UMP; AMP; program Amber9; molecular modelling; spectroscopy

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