Molecular Determinants of Ligand Binding Modes in the Histamine H4Receptor: Linking Ligand-Based Three-Dimensional Quantitative Structure–Activity Relationship (3D-QSAR) Models to in Silico Guided Receptor Mutagenesis Studies

2011 ◽  
Vol 54 (23) ◽  
pp. 8136-8147 ◽  
Author(s):  
Enade P. Istyastono ◽  
Saskia Nijmeijer ◽  
Herman D. Lim ◽  
Andrea van de Stolpe ◽  
Luc Roumen ◽  
...  
Keyword(s):  
Ligand Binding ◽  
In Silico ◽  
Three Dimensional ◽  
3D Qsar ◽  
Quantitative Structure Activity Relationship ◽  
Binding Modes ◽  
Quantitative Structure ◽  
Structure Activity ◽  
Molecular Determinants ◽  
Qsar Models

Computational Atom-based Three-Dimensional Quantitative Structure-Activity Relationship (3D QSAR) Model for Predicting Anti-Dengue Agents

2021 ◽  
Vol 16 (10) ◽  
pp. 50-58
Author(s):  
Ali Qusay Khalid ◽  
Vasudeva Rao Avupati ◽  
Husniza Hussain ◽  
Tabarek Najeeb Zaidan
Keyword(s):  
Dengue Fever ◽  
Three Dimensional ◽  
3D Qsar ◽  
Qsar Model ◽  
Quantitative Structure Activity Relationship ◽  
Activity Relationship ◽  
Quantitative Structure ◽  
Contour Maps ◽  
Structure Activity ◽  
Bioactive Ligands

Dengue fever is a viral infection spread by the female mosquito Aedes aegypti. It is a virus spread by mosquitoes found all over the tropics with risk levels varying depending on rainfall, relative humidity, temperature and urbanization. There are no specific medications that can be used to treat the condition. The development of possible bioactive ligands to combat Dengue fever before it becomes a pandemic is a global priority. Few studies on building three-dimensional quantitative structure-activity relationship (3D QSAR) models for anti-dengue agents have been reported. Thus, we aimed at building a statistically validated atom-based 3D-QSAR model using bioactive ligands reported to possess significant anti-dengue properties. In this study, the Schrodinger PhaseTM atom-based 3D QSAR model was developed and was validated using known anti-dengue properties as ligand data. This model was also tested to see if there was a link between structural characteristics and anti-dengue activity of a series of 3-acyl-indole derivatives. The established 3D QSAR model has strong predictive capacity and is statistically significant [Model: R2 Training Set = 0.93, Q2 (R2 Test Set) = 0.72]. In addition, the pharmacophore characteristics essential for the reported anti-dengue properties were explored using combined effects contour maps (coloured contour maps: blue: positive potential and red: negative potential) of the model. In the pathway of anti-dengue drug development, the model could be included as a virtual screening method to predict novel hits.

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