NMR Studies of Protein Ligand Interactions

1994 ◽  
pp. 115-154 ◽  
Author(s):  
J Feeney
Keyword(s):  
Nmr Studies ◽  
Protein Ligand Interactions ◽  
Ligand Interactions

NMR investigation of protein–ligand interactions for G-protein coupled receptors

2019 ◽  
Vol 11 (14) ◽  
pp. 1811-1825 ◽  
Author(s):  
Claire Raingeval ◽  
Isabelle Krimm
Keyword(s):  
Conformational Changes ◽  
Functional Characterization ◽  
Allosteric Modulation ◽  
G Protein Coupled Receptors ◽  
Nmr Studies ◽  
Protein Ligand Interactions ◽  
Ligand Interactions ◽  
Therapeutic Compounds ◽  
G Protein Coupled

In this review, we report NMR studies of ligand–GPCR interactions, including both ligand-observed and protein-observed NMR experiments. Published studies exemplify how NMR can be used as a powerful tool to design novel GPCR ligands and investigate the ligand-induced conformational changes of GPCRs. The strength of NMR also lies in its capability to explore the diverse signaling pathways and probe the allosteric modulation of these highly dynamic receptors. By offering unique opportunities for the identification, structural and functional characterization of GPCR ligands, NMR will likely play a major role for the generation of novel molecules both as new tools for the understanding of the GPCR function and as therapeutic compounds for a large diversity of pathologies.

NMR Studies of Protein–Ligand Interactions

2011 ◽  
pp. 233-259 ◽  
Author(s):  
Michael Goldflam ◽  
Teresa Tarragó ◽  
Margarida Gairí ◽  
Ernest Giralt
Keyword(s):  
Nmr Studies ◽  
Protein Ligand Interactions ◽  
Ligand Interactions

19F-NMR in Target-based Drug Discovery

2019 ◽  
Vol 26 (26) ◽  
pp. 4964-4983 ◽  
Author(s):  
CongBao Kang
Keyword(s):  
Drug Discovery ◽  
Conformational Changes ◽  
Protein Structures ◽  
19F Nmr ◽  
Binding Affinities ◽  
Protein Ligand Interactions ◽  
Compound Libraries ◽  
Ligand Interactions ◽  
Reference Ligand ◽  
Hit Identification

Solution NMR spectroscopy plays important roles in understanding protein structures, dynamics and protein-protein/ligand interactions. In a target-based drug discovery project, NMR can serve an important function in hit identification and lead optimization. Fluorine is a valuable probe for evaluating protein conformational changes and protein-ligand interactions. Accumulated studies demonstrate that 19F-NMR can play important roles in fragment- based drug discovery (FBDD) and probing protein-ligand interactions. This review summarizes the application of 19F-NMR in understanding protein-ligand interactions and drug discovery. Several examples are included to show the roles of 19F-NMR in confirming identified hits/leads in the drug discovery process. In addition to identifying hits from fluorinecontaining compound libraries, 19F-NMR will play an important role in drug discovery by providing a fast and robust way in novel hit identification. This technique can be used for ranking compounds with different binding affinities and is particularly useful for screening competitive compounds when a reference ligand is available.

Combiphore (Structure and Ligand Based Pharmacophore) - Approach for the Design of GPR40 Modulators in the Management of Diabetes

2020 ◽  
Vol 17 (2) ◽  
pp. 233-247
Author(s):  
Krishna A. Gajjar ◽  
Anuradha K. Gajjar
Keyword(s):  
Molecular Docking ◽  
Structural Information ◽  
Docking Studies ◽  
Structural Motif ◽  
Roc Curve Analysis ◽  
Ligand Complex ◽  
Discovery Studio ◽  
Protein Ligand Interactions ◽  
Ligand Interactions ◽  
Pharmacophore Models

Background: Pharmacophore mapping and molecular docking can be synergistically integrated to improve the drug design and discovery process. A rational strategy, combiphore approach, derived from the combined study of Structure and Ligand based pharmacophore has been described to identify novel GPR40 modulators. Methods: DISCOtech module from Discovery studio was used for the generation of the Structure and Ligand based pharmacophore models which gave hydrophobic aromatic, ring aromatic and negative ionizable as essential pharmacophoric features. The generated models were validated by screening active and inactive datasets, GH scoring and ROC curve analysis. The best model was exposed as a 3D query to screen the hits from databases like GLASS (GPCR-Ligand Association), GPCR SARfari and Mini-Maybridge. Various filters were applied to retrieve the hit molecules having good drug-like properties. A known protein structure of hGPR40 (pdb: 4PHU) having TAK-875 as ligand complex was used to perform the molecular docking studies; using SYBYL-X 1.2 software. Results and Conclusion: Clustering both the models gave RMSD of 0.89. Therefore, the present approach explored the maximum features by combining both ligand and structure based pharmacophore models. A common structural motif as identified in combiphore for GPR40 modulation consists of the para-substituted phenyl propionic acid scaffold. Therefore, the combiphore approach, whereby maximum structural information (from both ligand and biological protein) is explored, gives maximum insights into the plausible protein-ligand interactions and provides potential lead candidates as exemplified in this study.

Xanthine Oxidase and Transforming Growth Factor Beta-activated Kinase 1: potential Targets for Gout Intervention

2020 ◽  
Vol 16 ◽  
Author(s):  
Rajesh Basnet ◽  
Sandhya Khadka ◽  
Buddha Bahadur Basnet ◽  
Til Bahadur Basnet ◽  
Buddhi Bal Chidi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Xanthine Oxidase ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Developed Countries ◽  
Structure Based Drug Design ◽  
Protein Ligand Interactions ◽  
Ligand Interactions ◽  
Moderate Condition ◽  
Growth Factor Beta

Background: Gout, an inflammatory arthritis, caused by the deposition of monosodium urate crystals into affected joints and other tissues has become one of the major health problems of today's world. The main risk factor for gout is hyperuricemia, which may be caused by excessive or insufficient excretion of uric acid. The incidence is usually in the age group of 30- 50 years, commonly in males. In developed countries, the incidence of gout ranges from 1 to 4%. Despite effective treatments, there has been an increase in the number of cases over the past few decades. Objective: In recent years, the development of targeted drugs in gout has made significant achievements. The global impact of gout continues to increase, and as a result, the focus of disease-modifying therapies remains elusive. In addition, the characterization of available instrumental compounds is urgently needed to explore the use of novel selective and key protein-ligand interactions for the effective treatment of gout. Xanthine oxidase (XO) is a key target in gout to consider the use of XO inhibitors in patients with mild to moderate condition, however, the costs are high and no other direct progress has been made. Despite many XO inhibitors, a selective potent inhibitor for XO is limited. Likewise, in recent years, attention has been focused on different strategies for the discovery and development of new selectivity ligands against transforming growth factor beta-activated kinase 1 (TAK1), a potential therapeutic target for gout. Therefore the insight on human XO structure and TAK1 provides a clue into protein-ligand interactions and provides the basis for molecular modeling and structure-based drug design. Conclusion: In this review, we briefly introduce the clinical characteristics, the development of crystal, inhibitors, and crystal structure of XO and TAK1 protein.

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