Serine/Threonine Protein Kinases as Attractive Targets for Anti-Cancer Drugs—An Innovative Approach to Ligand Tuning Using Combined Quantum Chemical Calculations, Molecular Docking, Molecular Dynamic Simulations, and Network-like Similarity Graphs DOI Creative Commons
Magdalena Latosińska, Jolanta Natalia Latosińska

Molecules, Journal Year: 2024, Volume and Issue: 29(13), P. 3199 - 3199

Published: July 5, 2024

Serine/threonine protein kinases (CK2, PIM-1, RIO1) are constitutively active, highly conserved, pleiotropic, and multifunctional kinases, which control several signaling pathways regulate many cellular functions, such as cell activity, survival, proliferation, apoptosis. Over the past decades, they have gained increasing attention potential therapeutic targets, ranging from various cancers neurological, inflammation, autoimmune disorders to viral diseases, including COVID-19. Despite accumulation of a vast amount experimental data, there is still no “recipe” that would facilitate search for new effective kinase inhibitors. The aim our study was develop an screening method be useful this purpose. A combination Density Functional Theory calculations molecular docking, supplemented with newly developed quantitative methods comparison binding modes, provided deep insight into set desirable properties responsible their inhibition. mathematical metrics helped assess distance between while heatmaps revealed locations in ligand should modified according site requirements. Structure-Binding Affinity Index Structural-Binding Landscape proposed paper measure extent affinity or lost response relatively small change ligand’s structure. physico-chemical profile aforementioned factors enabled identification both “dead” “promising” directions. Tests carried out on data validated demonstrated high efficiency innovative approach. Our quantifying differences ligands capabilities holds promise guiding future research anti-cancer agents.

Language: Английский

Serine/Threonine Protein Kinases as Attractive Targets for Anti-Cancer Drugs—An Innovative Approach to Ligand Tuning Using Combined Quantum Chemical Calculations, Molecular Docking, Molecular Dynamic Simulations, and Network-like Similarity Graphs DOI Creative Commons
Magdalena Latosińska, Jolanta Natalia Latosińska

Molecules, Journal Year: 2024, Volume and Issue: 29(13), P. 3199 - 3199

Published: July 5, 2024

Serine/threonine protein kinases (CK2, PIM-1, RIO1) are constitutively active, highly conserved, pleiotropic, and multifunctional kinases, which control several signaling pathways regulate many cellular functions, such as cell activity, survival, proliferation, apoptosis. Over the past decades, they have gained increasing attention potential therapeutic targets, ranging from various cancers neurological, inflammation, autoimmune disorders to viral diseases, including COVID-19. Despite accumulation of a vast amount experimental data, there is still no “recipe” that would facilitate search for new effective kinase inhibitors. The aim our study was develop an screening method be useful this purpose. A combination Density Functional Theory calculations molecular docking, supplemented with newly developed quantitative methods comparison binding modes, provided deep insight into set desirable properties responsible their inhibition. mathematical metrics helped assess distance between while heatmaps revealed locations in ligand should modified according site requirements. Structure-Binding Affinity Index Structural-Binding Landscape proposed paper measure extent affinity or lost response relatively small change ligand’s structure. physico-chemical profile aforementioned factors enabled identification both “dead” “promising” directions. Tests carried out on data validated demonstrated high efficiency innovative approach. Our quantifying differences ligands capabilities holds promise guiding future research anti-cancer agents.

Language: Английский

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