Leveraging the Fragment Molecular Orbital Method to Explore the PLK1 Kinase Binding Site and Polo-Box Domain for Potent Small-Molecule Drug Design DOI Open Access
Haiyan Jin, Jongwan Kim,

Onju Lee

et al.

Published: Sept. 19, 2023

Polo-like kinase 1 (PLK1) plays a pivotal role in cell division regulation and emerges as promising therapeutic target for cancer treatment. Consequently, the development of small-molecule inhibitors targeting PLK1 has become focal point contemporary research. The adenosine triphosphate (ATP)-binding site polo-box domain present crucial interaction sites these inhibitors, aiming to disrupt protein's function. However, designing potent selective can be challenging, requiring deep understanding protein-ligand mechanisms at binding sites. In this context, our study leverages fragment molecular orbital (FMO) method explore site-specific interactions in-depth. Through FMO approach, we used elucidate drug design that are both selective. Our investigation further entailed comparative analysis various each characterized by distinct structural attributes. This comparison enhanced structure-activity relationships underscoring efficacy identifying critical features predicting modes ligands. Furthermore, research spotlighted "hot spot" residues instrumental robust binding. findings offer profound insights, priming rational innovative potential with significant implications developing anticancer therapeutics.

Language: Английский

Leveraging the Fragment Molecular Orbital Method to Explore the PLK1 Kinase Binding Site and Polo-Box Domain for Potent Small-Molecule Drug Design DOI Open Access
Haiyan Jin, Jongwan Kim,

Onju Lee

et al.

Published: Sept. 19, 2023

Polo-like kinase 1 (PLK1) plays a pivotal role in cell division regulation and emerges as promising therapeutic target for cancer treatment. Consequently, the development of small-molecule inhibitors targeting PLK1 has become focal point contemporary research. The adenosine triphosphate (ATP)-binding site polo-box domain present crucial interaction sites these inhibitors, aiming to disrupt protein's function. However, designing potent selective can be challenging, requiring deep understanding protein-ligand mechanisms at binding sites. In this context, our study leverages fragment molecular orbital (FMO) method explore site-specific interactions in-depth. Through FMO approach, we used elucidate drug design that are both selective. Our investigation further entailed comparative analysis various each characterized by distinct structural attributes. This comparison enhanced structure-activity relationships underscoring efficacy identifying critical features predicting modes ligands. Furthermore, research spotlighted "hot spot" residues instrumental robust binding. findings offer profound insights, priming rational innovative potential with significant implications developing anticancer therapeutics.

Language: Английский

Citations

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