Optimization of molecular modeling strategies for challenging blind docking

Date

2024-8-15

Author

Sekkin, Ecem

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This thesis explores two distinct biological structures, each presenting unique challenges that cannot be addressed through conventional methods. The first study focuses on the spike protein of SARS-CoV-2 and a peptide-based drug candidate designed by our collaborator, investigating the potential interactions between the protein and the ligand across four different binding sites. The second study examines recently discovered quadruplex-duplex hybrids (PDB ID: 7CV3-7CV4) in the PIM1 oncogene, proposed as potential targets. Known G-quadruplex stabilizer ligands such as Doxorubicin, Braco-19, and RHPS4 are analyzed to provide insights into their binding modes with these quadruplex-duplex hybrids. Molecular docking techniques are enhanced by integrating molecular mechanics calculations using the newly developed software bioAIM from Meddenovo. This software analyzes interaction energies and conformational changes to improve our understanding of ligand-target interactions. Molecular docking studies reveal promising interactions at multiple binding sites on the spike protein, with one site showing significant potential for drug binding. G-quadruplex ligands primarily bind at the Quadruplex-Duplex junction, suggesting the need for further investigation into the impact of G-quadruplex DNA on drug binding. These findings will guide the design and development of new-generation drugs or the re-purposing of existing drugs for these targets.

Subject Keywords

Molecular Docking, SARS-CoV-2, G-Quadruplex, Therapeutics

URI

https://hdl.handle.net/11511/111269

Collections

Graduate School of Natural and Applied Sciences, Thesis