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Title

Insights into Molecular Interactions of human Wnt5b and Frizzled proteins for their role in teratogenicity

 

Authors

Sween Dahiya, Vandana Saini, Pawan Kumar & Ajit Kumar*

 

Affiliation

Toxicology and Computational Biology Group, Centre for Bioinformatics; M. D. University, Rohtak, Haryana 124 001, India

 

Email

Ajit Kumar E-mail: akumar.cbt.mdu@gmail.com; *Corresponding author

 

Article Type

Research Article

 

Date

Received March 16, 2018; Accepted March 23, 2018; Published April 15, 2019

 

Abstract

Wnt-Fzd signalling plays vital role in different physiological pathways including embryonic development and supposed to be probable target of many teratogens. The present study was done to investigate the role of human Wnt5b interaction with different isoforms of human Fzds and also the molecular interactions of their complexes with selected known teratogens [Carbamazepine (CBZ), Retinoic acid (RA), Valproic acid (VPA), Aminopterin (AMP) and Phenytoin (PHY)] using Niclosamide (NLM) as standard. The models of hWnt5b and hFzd isoforms, whose solved crystal structures were unavailable, were generated using homology modeling and hWnt5b was subjected to protein-protein docking studies against different isoforms of hFzd. The macromolecular docking studies of hWnt5b-hFzds complexes revealed that hWnt5b had highest binding affinity with hFzd8 and lowest with hFzd1, respectively. The Cysteine rich domain (CRD) of hFzds docked against hWnt5b into a palm shaped opening or near the largest binding pocket as in hWnt5b-hFzd6. The possible role of Wnt-Fzd interactions in developmental toxicity due to selected teratogens were also investigated using molecular docking studies which showed that Retinoic Acid possessed the maximum binding affinity with binding energy of for hWnt5b-hFzd8 complex while VPA was observed to have lowest binding affinity towards all the studied hWnt5b-hFzd complexes.

 

Keywords

Frizzled; homology modeling; molecular docking; fetal development

 

Citation

Dahiya et al. Bioinformation 15(4): 246-254 (2019)

 

Edited by

P Kangueane

 

ISSN

0973-2063

 

Publisher

Biomedical Informatics

 

License

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.