title: Homology modelling and molecular docking studies of human placental cadherin protein for its role in teratogenic effects of anti-epileptic drugs.
abstract: 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.
authors.affiliation: Toxicology and Computational Biology Group, Centre for Bioinformatics, M.D. University, Rohtak, Haryana 124001, India.
authors.forename: Sakshi
authors.initials: S
authors.lastname: Piplani
authors.affiliation: Toxicology and Computational Biology Group, Centre for Bioinformatics, M.D. University, Rohtak, Haryana 124001, India.
authors.forename: Vandana
authors.initials: V
authors.lastname: Saini
authors.affiliation: Toxicology and Computational Biology Group, Centre for Bioinformatics, M.D. University, Rohtak, Haryana 124001, India.
authors.forename: Ravi Ranjan K
authors.initials: RR
authors.lastname: Niraj
authors.affiliation: Toxicology and Computational Biology Group, Centre for Bioinformatics, M.D. University, Rohtak, Haryana 124001, India.
authors.forename: Adya
authors.initials: A
authors.lastname: Pushp
authors.affiliation: Toxicology and Computational Biology Group, Centre for Bioinformatics, M.D. University, Rohtak, Haryana 124001, India. Electronic address: akumar.cbt.mdu@gmail.com.
authors.forename: Ajit
authors.initials: A
authors.lastname: Kumar
mesh_terms: D000081:Acetamides / Q000737:chemistry; D000588:Amines / Q000737:chemistry; D000818:Animals; D000927:Anticonvulsants / Q000737:chemistry*; D001665:Binding Sites; D015820:Cadherins / Q000737:chemistry*; D002118:Calcium / Q000737:chemistry; D002413:Cations, Divalent; D003509:Cyclohexanecarboxylic Acids / Q000737:chemistry; D005260:Female; D000077206:Gabapentin; D006801:Humans; D051379:Mice; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D000069583:Pregabalin / Q000737:chemistry; D011247:Pregnancy; D017385:Sequence Homology; D013723:Teratogens / Q000737:chemistry*; D020888:Vigabatrin / Q000737:chemistry; D005680:gamma-Aminobutyric Acid / Q000737:chemistry
chemical_list: D000081:Acetamides; D000588:Amines; D000927:Anticonvulsants; C512197:CDH3 protein, human; D015820:Cadherins; D002413:Cations, Divalent; D003509:Cyclohexanecarboxylic Acids; D013723:Teratogens; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; C067553:remacemide; D020888:Vigabatrin; D002118:Calcium
keywords: AEDs; Cadherin; Docking; Homology Modelling; MD simulation; Teratogenicity