Quartz Crystal Microbalance with Monitoring (QCM-D): Preparing Lipid Layers for the Study of Complex Protein–Ligand Interactions

2021 ◽  
pp. 183-197
Author(s):  
Holly L. Birchenough ◽  
Thomas A. Jowitt
Keyword(s):  
Quartz Crystal Microbalance ◽  
Quartz Crystal ◽  
Protein Ligand Interactions ◽  
Complex Protein ◽  
Ligand Interactions ◽  
Lipid Layers

scholarly journals Natural compounds as potential PI3K-AKT1 signaling pathway inhibitors by means of pharmacophore modeling

2016 ◽  
Author(s):  
Serena Dotolo ◽  
Angelo Gaeta ◽  
Angelo Facchiano
Keyword(s):  
Protein Interactions ◽  
Chemical Properties ◽  
Natural Compounds ◽  
Pharmacophore Modeling ◽  
Bioactive Molecules ◽  
Allosteric Inhibitors ◽  
Protein Ligand Interactions ◽  
Zinc Database ◽  
Complex Protein ◽  
Ligand Interactions

AKT1, a modulator of PI3K-AKT1 pathway, is dysregulated in several human diseases, and understanding deeper its role in the complexity of biological systems remains an important goal. The research has been focused on development and study of potential synthetic-natural allosteric inhibitors for AKT1, and recent studies have shown how some natural compounds may play this role (1). We are interested in a screening of small bioactive molecules, in order to identify the potential “lead compounds”, for next experimental assays, searching those potentially able to inhibit AKT1 and its signaling mechanisms, trying to re-establish the normal balance and safeguarding of human health. The workflow executed is the following: 1) search in PDB database of a model structure for AKT1 (comparing different structures and choosing the most suitable for our purposes), through algorithm BLAST. 2) pharmacophore modeling by means of ZINCpharmer web-server, to investigate all purchasable compounds of the ZINC database, using the Pharmer as efficient and exact pharmacophore search technology (2). 3) screening of possible natural AKT1 inhibitors, using the pharmacophore generated by ZINCpharmer, choosing only the best candidates for next steps. 4) molecular validation of selected compounds, to analyze the ligand-protein interactions. 5) study of physical-chemical properties of selected compounds to trace their origin. 6)prediction of their biosynthetic pathways and Pharmacokinetics/Pharmacodynamics models, by means of ADMET/toxicity predictor server in order to direct the design of next experimental assays. Our attention is focused on the study of natural compounds that can show many health benefits, through the realization and analysis of “pharmacophore modeling”, essential step in drug discovery (3). We selected the PDB structure 3O96 as the reference complex (protein-ligand), and we analyzed it by means of ZINCpharmer, to generate three different “pharmacophore models” with three different list of natural compounds. It is performed a thorough screening of compounds applying other filters, to find some good candidates as possible natural AKT1 allosteric inhibitors. The compounds that match a well-defined pharmacophore have been analyzed through direct molecular docking, for selecting only the best candidates and studying the protein-ligand interactions. Selected compounds have been investigated in more details, to trace their origin, by their chemical-physical properties. This information can help us to predict some plausible enzyme-catalyzed reaction pathways, investigated with PathPred server and KEGG compound database, in order to highlight the most important reactions for biosynthesis of compounds and obtain PharmacoKinetics/PharmacoDynamics (PK/PD) models through ADME predictor server and to realize of next experimental assays. (Abstract truncated at 3,000 characters - the full version is available in the pdf file)

scholarly journals Natural compounds as potential PI3K-AKT1 signaling pathway inhibitors by means of pharmacophore modeling

2016 ◽  
Author(s):  
Serena Dotolo ◽  
Angelo Gaeta ◽  
Angelo Facchiano
Keyword(s):  
Protein Interactions ◽  
Chemical Properties ◽  
Natural Compounds ◽  
Pharmacophore Modeling ◽  
Bioactive Molecules ◽  
Allosteric Inhibitors ◽  
Protein Ligand Interactions ◽  
Zinc Database ◽  
Complex Protein ◽  
Ligand Interactions

AKT1, a modulator of PI3K-AKT1 pathway, is dysregulated in several human diseases, and understanding deeper its role in the complexity of biological systems remains an important goal. The research has been focused on development and study of potential synthetic-natural allosteric inhibitors for AKT1, and recent studies have shown how some natural compounds may play this role (1). We are interested in a screening of small bioactive molecules, in order to identify the potential “lead compounds”, for next experimental assays, searching those potentially able to inhibit AKT1 and its signaling mechanisms, trying to re-establish the normal balance and safeguarding of human health. The workflow executed is the following: 1) search in PDB database of a model structure for AKT1 (comparing different structures and choosing the most suitable for our purposes), through algorithm BLAST. 2) pharmacophore modeling by means of ZINCpharmer web-server, to investigate all purchasable compounds of the ZINC database, using the Pharmer as efficient and exact pharmacophore search technology (2). 3) screening of possible natural AKT1 inhibitors, using the pharmacophore generated by ZINCpharmer, choosing only the best candidates for next steps. 4) molecular validation of selected compounds, to analyze the ligand-protein interactions. 5) study of physical-chemical properties of selected compounds to trace their origin. 6)prediction of their biosynthetic pathways and Pharmacokinetics/Pharmacodynamics models, by means of ADMET/toxicity predictor server in order to direct the design of next experimental assays. Our attention is focused on the study of natural compounds that can show many health benefits, through the realization and analysis of “pharmacophore modeling”, essential step in drug discovery (3). We selected the PDB structure 3O96 as the reference complex (protein-ligand), and we analyzed it by means of ZINCpharmer, to generate three different “pharmacophore models” with three different list of natural compounds. It is performed a thorough screening of compounds applying other filters, to find some good candidates as possible natural AKT1 allosteric inhibitors. The compounds that match a well-defined pharmacophore have been analyzed through direct molecular docking, for selecting only the best candidates and studying the protein-ligand interactions. Selected compounds have been investigated in more details, to trace their origin, by their chemical-physical properties. This information can help us to predict some plausible enzyme-catalyzed reaction pathways, investigated with PathPred server and KEGG compound database, in order to highlight the most important reactions for biosynthesis of compounds and obtain PharmacoKinetics/PharmacoDynamics (PK/PD) models through ADME predictor server and to realize of next experimental assays. (Abstract truncated at 3,000 characters - the full version is available in the pdf file)

IgG binding kinetics to oligo B protein A domains on lipid layers immobilized on a 27 MHz quartz-crystal microbalance

2007 ◽  
Vol 20 (2) ◽  
pp. 83-89 ◽  
Author(s):  
Hideyuki Mitomo ◽  
Hideki Shigematsu ◽  
Eiry Kobatake ◽  
Hiroyuki Furusawa ◽  
Yoshio Okahata
Keyword(s):  
Quartz Crystal Microbalance ◽  
Quartz Crystal ◽  
Protein A ◽  
Binding Kinetics ◽  
Igg Binding ◽  
A Domains ◽  
Lipid Layers

Evaluation of a PAH/PSS Layer-by-Layer Deposited Film Using a Quartz-Crystal-Microbalance and Surface-Plasmon-Resonance Hybrid Sensor

2015 ◽  
Vol E98.C (2) ◽  
pp. 136-138 ◽  
Author(s):  
Keisuke KAWACHI ◽  
Kazunari SHINBO ◽  
Yasuo OHDAIRA ◽  
Akira BABA ◽  
Keizo KATO ◽  
...  
Keyword(s):  
Surface Plasmon Resonance ◽  
Surface Plasmon ◽  
Quartz Crystal Microbalance ◽  
Plasmon Resonance ◽  
Quartz Crystal ◽  
Layer By Layer ◽  
Deposited Film ◽  
Resonance Hybrid

Interaction of Clear Flavor Emulsions Containing Lemon Essential Oils with Lipid Bilayers via a Quartz Crystal Microbalance

2019 ◽  
Vol 25 (6) ◽  
pp. 879-884
Author(s):  
Takahiro Sakai ◽  
Hayato Seki ◽  
Shogo Yoshida ◽  
Hayato Hori ◽  
Hisashi Suzuki ◽  
...  
Keyword(s):  
Essential Oils ◽  
Lipid Bilayers ◽  
Quartz Crystal Microbalance ◽  
Quartz Crystal

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.

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