fulltext.study @t Gmail

Homology modelling and molecular docking studies of human placental cadherin protein for its role in teratogenic effects of anti-epileptic drugs

Paper ID Volume ID Publish Year Pages File Format Full-Text
14957 1363 2016 8 PDF Available
Title
Homology modelling and molecular docking studies of human placental cadherin protein for its role in teratogenic effects of anti-epileptic drugs
Abstract

•Teratogenic effects of AEDs is predicted to be elevated when the pregnant woman is subjected to Ca-rich diet or Ca-supplements.•hp-Cadherin is involved in teratogenic effects caused by 04 major marketed AEDs- Gabapentin, Pregabalin, Remacimide and Vigabatrin.•hp-Cadherin is observed to have negligible role in the teratogenic effects of VPA.•The major binding pockets for AEDs in hp-cadherin are, in general composed of charged, polar and aliphatic amino acids like Isoleucine, Tyrosine, Glutamate etc.•Observation beckons a novel biochemical link of AEDs teratogenicity with placental cadherin and invites further investigation.

Anti-epileptic drugs (AEDs) have high risk of teratogenic side effects, including neural tube defects while mother is on AEDs for her own prevention of convulsions during pregnancy. The present study investigated the interaction of major marketed AEDs and human placental (hp)-cadherin protein, in-silico, to establish the role of hp-cadherin protein in teratogenicity and also to evaluate the importance of Ca2+ ion in functioning of the protein. A set of 21 major marketed AEDs were selected for the study and 3D-structure of hp-cadherin was constructed using homology modelling and energy minimized using MD simulations. Molecular docking studies were carried out using selected AEDs as ligand with hp-cadherin (free and bound Ca2+ ion) to study the behavioural changes in hp-cadherin due to presence of Ca2+ ion. The study reflected that four AEDs (Gabapentin, Pregabalin, Remacimide and Vigabatrine) had very high affinity towards hp-cadherin and thus the later may have prominent role in the teratogenic effects of these AEDs. From docking simulation analysis it was observed that Ca2+ ion is required to make hp-cadherin energetically favourable and sterically functional.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide

Keywords
AEDs, anti-epileptic drugs; AMBER, assisted model building with energy refinement; GUI, graphical user interface; GROMOS, GROningen molecular simulation; VPA, valproic acid; MD, molecular dynamicsCadherin; AEDs; Docking; MD simulation; Homology Modelling;
First Page Preview
Homology modelling and molecular docking studies of human placental cadherin protein for its role in teratogenic effects of anti-epileptic drugs
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us
Publisher
Database: Elsevier - ScienceDirect
Journal: Computational Biology and Chemistry - Volume 60, February 2016, Pages 1–8
Authors
, , , , ,
Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us