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

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 Ca(2+) 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 Ca(2+) ion) to study the behavioural changes in hp-cadherin due to presence of Ca(2+) 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 Ca(2+) ion is required to make hp-cadherin energetically favourable and sterically functional.

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