Enhanced Binding Site Identification in Protein–Ligand Complexes with a Combined Blind Docking and Dipolar Electron Paramagnetic Resonance Approach DOI
M.I. Kolokolov, Natalya E. Sannikova,

Sergei A. Dementev

et al.

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: April 11, 2025

Understanding protein-drug complex structures is crucial for elucidating therapeutic mechanisms and side effects. Blind docking facilitates site identification but hindered by computational complexity imprecise scoring, causing ambiguity. Dipolar electron paramagnetic resonance (EPR) provides spin-spin distances struggles to determine relative positions within complexes. We present a novel approach combining GPU-accelerated blind with EPR distance constraints enhance binding detection. Our algorithm uses single distribution filter validate results. Ligand poses from are clustered, filtered expected distances, refined through focused docking. To illustrate our approach, we investigated human serum albumin porphyrin-based photosensitizers used in photodynamic therapy. Combining EPR, identified possible sites, demonstrating that data significantly reduce configurations provide experimentally validated information. This strategy produces detailed map of photoligand revealing may occur away standard sites often involves multiple locations. Furthermore, it overcomes key limitations fluorescence-based methods, which prone misinterpretation studies due non one-to-one donor-acceptor relationships. By resolving ambiguities both framework versatile platform investigating EPR-active ligands.

Language: Английский

Rigid and stable nitroxide spin label for high-resolution distance measurements on proteins by DEER experiments DOI Creative Commons
Yating Chen,

Xing Zhang,

Jia‐Liang Chen

et al.

Magnetic Resonance Letters, Journal Year: 2025, Volume and Issue: unknown, P. 200194 - 200194

Published: Feb. 1, 2025

Language: Английский

Citations

0
Enhanced Binding Site Identification in Protein–Ligand Complexes with a Combined Blind Docking and Dipolar Electron Paramagnetic Resonance Approach DOI
M.I. Kolokolov, Natalya E. Sannikova,

Sergei A. Dementev

et al.

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: April 11, 2025

Understanding protein-drug complex structures is crucial for elucidating therapeutic mechanisms and side effects. Blind docking facilitates site identification but hindered by computational complexity imprecise scoring, causing ambiguity. Dipolar electron paramagnetic resonance (EPR) provides spin-spin distances struggles to determine relative positions within complexes. We present a novel approach combining GPU-accelerated blind with EPR distance constraints enhance binding detection. Our algorithm uses single distribution filter validate results. Ligand poses from are clustered, filtered expected distances, refined through focused docking. To illustrate our approach, we investigated human serum albumin porphyrin-based photosensitizers used in photodynamic therapy. Combining EPR, identified possible sites, demonstrating that data significantly reduce configurations provide experimentally validated information. This strategy produces detailed map of photoligand revealing may occur away standard sites often involves multiple locations. Furthermore, it overcomes key limitations fluorescence-based methods, which prone misinterpretation studies due non one-to-one donor-acceptor relationships. By resolving ambiguities both framework versatile platform investigating EPR-active ligands.

Language: Английский

Citations

0