Exploring the intercalation binding of tiamulin with DNA using multispectroscopy and a molecular modelling approach

Area of Science:

• Biochemistry
• Molecular Biology
• Biophysical Chemistry

Background:

• Understanding drug-DNA interactions is crucial for developing novel therapeutics.
• Tiamulin is an antibiotic with potential DNA-binding properties that require elucidation.

Purpose of the Study:

• To investigate the binding mechanism of tiamulin with calf thymus DNA.
• To characterize the biophysical changes in DNA upon tiamulin interaction.
• To determine the binding mode and affinity of tiamulin to DNA.

Main Methods:

• Multispectroscopic techniques (viscosity, melting temperature, fluorescence, circular dichroism).
• Molecular modeling simulations.
• Ionic strength variation studies.

Main Results:

• Tiamulin binding increased DNA viscosity and melting temperature.
• Fluorescence intensity remained stable across varying ionic strengths.
• Tiamulin exhibited higher binding affinity for single-stranded DNA (ssDNA) than double-stranded DNA (dsDNA).
• Circular dichroism spectra indicated a loosening of DNA helix structure and enhanced base stacking.
• Molecular modeling confirmed intercalation of tiamulin into DNA base pairs via van der Waals forces and hydrogen bonds, with a binding free energy of -18.73 kJ/mol.

Conclusions:

• Tiamulin interacts with calf thymus DNA through intercalation.
• The interaction is stronger with ssDNA compared to dsDNA.
• The findings provide insights into the molecular mechanism of tiamulin-DNA complex formation.