Structural studies on ligand–DNA systems: A robust approach in drug design.
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Date
2012-07
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Abstract
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.
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Keywords
Fluorescence, ligand–DNA binding, molecular docking, NMR spectroscopy
Citation
Kumar Surat, Pandya Prateek, Pandav Kumud, Gupta Surendra P, Chopra Arun. Structural studies on ligand–DNA systems: A robust approach in drug design. Journal of Biosciences. 2012 July; 37 (3): 553-561.