Investigation of protein-ligand complexes by ligand-based NMR methods.

Autor: Di Carluccio C; Dipartimento di Scienze Chimiche, Complesso Universitario Monte Sant'Angelo, Università di Napoli Federico II, Via Cintia 4, I-80126, Napoli, Italy., Forgione MC; Dipartimento di Scienze Chimiche, Complesso Universitario Monte Sant'Angelo, Università di Napoli Federico II, Via Cintia 4, I-80126, Napoli, Italy; GSK, Via Fiorentina 1, 53100, Siena, Italy., Martini S; GSK, Via Fiorentina 1, 53100, Siena, Italy., Berti F; GSK, Via Fiorentina 1, 53100, Siena, Italy., Molinaro A; Dipartimento di Scienze Chimiche, Complesso Universitario Monte Sant'Angelo, Università di Napoli Federico II, Via Cintia 4, I-80126, Napoli, Italy., Marchetti R; Dipartimento di Scienze Chimiche, Complesso Universitario Monte Sant'Angelo, Università di Napoli Federico II, Via Cintia 4, I-80126, Napoli, Italy. Electronic address: roberta.marchetti@unina.it., Silipo A; Dipartimento di Scienze Chimiche, Complesso Universitario Monte Sant'Angelo, Università di Napoli Federico II, Via Cintia 4, I-80126, Napoli, Italy; CNR, Institute for Polymers, Composites and Biomaterials, IPCB ss, Catania, Italy. Electronic address: silipo@unina.it.
Jazyk: angličtina
Zdroj: Carbohydrate research [Carbohydr Res] 2021 May; Vol. 503, pp. 108313. Date of Electronic Publication: 2021 Apr 09.
DOI: 10.1016/j.carres.2021.108313
Abstrakt: Molecular recognition is at the base of all biological events and its knowledge at atomic level is pivotal in the development of new drug design approaches. NMR spectroscopy is one of the most widely used technique to detect and characterize transient ligand-receptor interactions in solution. In particular, ligand-based NMR approaches, including NOE-based NMR techniques, diffusion experiments and relaxation methods, are excellent tools to investigate how ligands interact with their receptors. Here we describe the key structural information that can be achieved on binding processes thanks to the combined used of advanced NMR and computational methods. Saturation Transfer Difference NMR (STD-NMR), WaterLOGSY, diffusion- and relaxation-based experiments, together with tr-NOE techniques allow, indeed, to investigate the ligand behavior when bound to a receptor, determining, among others, the epitope map of the ligand and its bioactive conformation. The combination of these NMR techniques with computational methods, including docking, molecular dynamics and CORCEMA-ST analysis, permits to define and validate an accurate 3D model of protein-ligand complexes.
(Copyright © 2021 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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