Exploring the Ligand Recognition Properties of the Human Vasopressin V1a Receptor Using QSAR and Molecular Modeling Studies

Vaptans are compounds that act as non‐peptide vasopressin receptor antagonists. These compounds have diverse chemical structures. In this study, we used a combined approach of protein folding, molecular dynamics simulations, docking, and quantitative structure–activity relationship (QSAR) to elucida...

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Bibliographic Details
Published in:Chemical biology & drug design 2014-02, Vol.83 (2), p.207-223
Main Authors: Contreras-Romo, Martha C., Martínez-Archundia, Marlet, Deeb, Omar, Ślusarz, Magdalena J., Ramírez-Salinas, Gema, Garduño-Juárez, Ramón, Quintanar-Stephano, Andrés, Ramírez-Galicia, Guillermo, Correa-Basurto, José
Format: Article
Language:English
Subjects:
Antidiuretic Hormone Receptor Antagonists
Benzodiazepines - chemistry
Binding Sites
docking
Humans
Hydrophobic and Hydrophilic Interactions
Ligands
MD simulations
Molecular Docking Simulation
Neural Networks (Computer)
Protein Structure, Tertiary
QSAR studies
Quantitative Structure-Activity Relationship
Receptors, Vasopressin - metabolism
V1aR
vaptans
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Summary:Vaptans are compounds that act as non‐peptide vasopressin receptor antagonists. These compounds have diverse chemical structures. In this study, we used a combined approach of protein folding, molecular dynamics simulations, docking, and quantitative structure–activity relationship (QSAR) to elucidate the detailed interaction of the vasopressin receptor V1a (V1aR) with some of its blockers (134). QSAR studies were performed using MLR analysis and were gathered into one group to perform an artificial neural network (ANN) analysis. For each molecule, 1481 molecular descriptors were calculated. Additionally, 15 quantum chemical descriptors were calculated. The final equation was developed by choosing the optimal combination of descriptors after removing the outliers. Molecular modeling enabled us to obtain a reliable tridimensional model of V1aR. The docking results indicated that the great majority of ligands reach the binding site under π–π, π–cation, and hydrophobic interactions. The QSAR studies demonstrated that the heteroatoms N and O are important for ligand recognition, which could explain the structural diversity of ligands that reach V1aR. Exploration of V1aR under theoretical studies (MD simulations, QSAR and docking studies) to depict the principal recognition properties which could be use for drug design.
ISSN:1747-0277
1747-0285
DOI:10.1111/cbdd.12229