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ABSTRACT
G-quadruplexes are non-canonical DNA structures that emerged as important drug targets. Andrographolide is a plant-derived compound with various pharmacological properties. The binding of andrographolide with CREB1 G-quadruplex and Thrombin Binding Aptamer (TBA) was estimated using molecular docking, dynamics, and simulation. The data demonstrated the stabilising effect of the ligand on G-quadruplexes. Andrographolide binds to the CREB1 G-quadruplex by forming hydrogen bonds with the terminal residues and thymine and cytosine residues in the loop region with a binding energy of – 7.30 kcal/mol. At the same time, the TBA G-quadruplex structure formed hydrogen bonds with the residues in the quartet and loop region with binding energy – 6.61 kcal/mol. The Molecular Mechanics Poisson-Boltzmann Surface Area analysis revealed that the contribution from electrostatic energy is higher (−109.21 ± 51.40 KJ/mol) for CREB1 than for TBA (−41.49 ± 27.25 KJ/mol). Principle component analysis illustrated that the eigenvalues are much higher for the unbound forms than for the ligand-bound forms. These findings indicate that andrographolide could potentially target G-quadruplex forming DNA sequences in various oncogenes and can have multiple therapeutic applications.
Acknowledgments
The authors greatly acknowledge the computational facility provided by the Institute Computer Center, Indian Institute of Technology Roorkee. Pallavi Agrawal acknowledges the Ministry of Human Resources and Development (MHRD), India for a research fellowship. Maya S Nair is grateful to the Council of Scientific and Industrial Research (CSIR), India for the partial funding of the work.
Disclosure statement
No potential conflict of interest was reported by the author(s).