Insights into the Allosteric Regulation of Human Hsp90 Revealed by NMR Spectroscopy DOI Creative Commons
Tjaša Goričan, Simona Golič Grdadolnik

Biomolecules, Journal Year: 2024, Volume and Issue: 15(1), P. 37 - 37

Published: Dec. 30, 2024

Human heat shock protein 90 (Hsp90) is one of the most important chaperones that play a role in late stages folding. Errors process chaperone cycle can lead to diseases such as cancer and neurodegenerative diseases. Therefore, activity Hsp90 must be carefully regulated. One possibilities allosteric regulation by its natural modulators-nucleotides, co-chaperones client proteins-and synthetic small-molecule modulators, those targeting middle domain or C-terminal (CTD) Hsp90. Since no experimentally determined structure modulator bound CTD human has yet been obtained, challenge for structure-based design modulators remains. Solution nuclear magnetic resonance (NMR) spectroscopy could utilized overcome these problems. The main aim this review article discuss how solution NMR techniques, especially protein-based, advanced isotope labeling proteins have used investigate cytosolic isoforms with modulators. This provides basis planning future experiments, gaining insights into sites mechanisms regulation.

Language: Английский

THE FUTURE OF PLANT LECTINOLOGY: ADVANCED TECHNOLOGIES AND COMPUTATIONAL TOOLS DOI Creative Commons
Vinicius José Silva Osterne, Kyria Santiago Nascimento, Benildo Sousa Cavada

et al.

BBA Advances, Journal Year: 2025, Volume and Issue: unknown, P. 100145 - 100145

Published: Jan. 1, 2025

Language: Английский

Citations

0
Use of AI-methods over MD simulations in the sampling of conformational ensembles in IDPs DOI Creative Commons

Souradeep Sil,

Ishita Datta,

Sankar Basu

et al.

Frontiers in Molecular Biosciences, Journal Year: 2025, Volume and Issue: 12

Published: April 8, 2025

Intrinsically Disordered Proteins (IDPs) challenge traditional structure-function paradigms by existing as dynamic ensembles rather than stable tertiary structures. Capturing these is critical to understanding their biological roles, yet Molecular Dynamics (MD) simulations, though accurate and widely used, are computationally expensive struggle sample rare, transient states. Artificial intelligence (AI) offers a transformative alternative, with deep learning (DL) enabling efficient scalable conformational sampling. They leverage large-scale datasets learn complex, non-linear, sequence-to-structure relationships, allowing for the modeling of in IDPs without constraints physics-based approaches. Such DL approaches have been shown outperform MD generating diverse comparable accuracy. Most models rely primarily on simulated data training experimental serves role validation, aligning generated observable physical biochemical properties. However, challenges remain, including dependence quality, limited interpretability, scalability larger proteins. Hybrid combining AI can bridge gaps integrating statistical thermodynamic feasibility. Future directions include incorporating observables into frameworks refine predictions enhance applicability. AI-driven methods hold significant promise IDP research, offering novel insights protein dynamics therapeutic targeting while overcoming limitations simulations.

Language: Английский

Citations

0
Artificial Intelligence–Driven Computational Approaches in the Development of Anticancer Drugs DOI Open Access
Pankaj Garg, G. D. Singhal, Prakash Kulkarni

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(22), P. 3884 - 3884

Published: Nov. 20, 2024

The integration of AI has revolutionized cancer drug development, transforming the landscape discovery through sophisticated computational techniques. AI-powered models and algorithms have enhanced computer-aided design (CADD), offering unprecedented precision in identifying potential anticancer compounds. Traditionally, been a complex, resource-intensive process, but introduces new opportunities to accelerate discovery, reduce costs, optimize efficiency. This manuscript delves into transformative applications AI-driven methodologies predicting developing drugs, critically evaluating their reshape future therapeutics while addressing challenges limitations.

Language: Английский

Citations

3
Insights into the Allosteric Regulation of Human Hsp90 Revealed by NMR Spectroscopy DOI Creative Commons
Tjaša Goričan, Simona Golič Grdadolnik

Biomolecules, Journal Year: 2024, Volume and Issue: 15(1), P. 37 - 37

Published: Dec. 30, 2024

Human heat shock protein 90 (Hsp90) is one of the most important chaperones that play a role in late stages folding. Errors process chaperone cycle can lead to diseases such as cancer and neurodegenerative diseases. Therefore, activity Hsp90 must be carefully regulated. One possibilities allosteric regulation by its natural modulators-nucleotides, co-chaperones client proteins-and synthetic small-molecule modulators, those targeting middle domain or C-terminal (CTD) Hsp90. Since no experimentally determined structure modulator bound CTD human has yet been obtained, challenge for structure-based design modulators remains. Solution nuclear magnetic resonance (NMR) spectroscopy could utilized overcome these problems. The main aim this review article discuss how solution NMR techniques, especially protein-based, advanced isotope labeling proteins have used investigate cytosolic isoforms with modulators. This provides basis planning future experiments, gaining insights into sites mechanisms regulation.

Language: Английский

Citations

0