Structural studies on ligand–DNA systems: A robust approach in drug design

Journal of biosciences

Kumud Pandav¹  Surat Kumar1¹  Arun Chopra²  Prateek Pandya¹  Surendra P Gupta¹ 

[1] Department of Chemistry, Dayalbagh Educational Institute, Dayalbagh, Agra 282 110, India$$;Department of Biotechnology, Hindustan College of Science and Technology, Farah 281 122, India$$

关键词: Fluorescence;    ligand–DNA binding;    molecular docking;    NMR spectroscopy;   

DOI  :  

来源: Indian Academy of Sciences

【 摘 要 】

Molecular docking, molecular mechanics, molecular dynamics and relaxation matrix simulation protocols have been extensively used to generate the structural details of ligand–receptor complexes in order to understand the binding interactions between the two entities. Experimental methods like NMR spectroscopy and X-ray crystallography are known to provide structural information about ligand–receptor complexes. In addition, fluorescence spectroscopy, circular dichroism (CD) spectroscopy and molecular docking have also been utilized to decode the phenomenon of the ligand–DNA interactions, with good correlation between experimental and computational results. The DNA binding affinity was demonstrated by analysing fluorescence spectral data. Structural rigidity of DNA upon ligand binding was identified by CD spectroscopy. Docking is carried out using the DNA-Dock program which results in the binding affinity data along with structural information like interatomic distances and H-bonding, etc. The complete structural analyses of various drug–DNA complexes have afforded results that indicate a specific DNA binding pattern of these ligands. It also exhibited that certain structural features of ligands can make a ligand to be AT- or GC-specific. It was also demonstrated that changing specificity from AT base pairs to GC base pairs further improved the DNA topoisomerase inhibiting activity in certain ligands. Thus, a specific molecular recognition signature encrypted in the structure of ligand can be decoded and can be effectively employed in designing more potent antiviral and antitumour agents.

【 授权许可】

Unknown