AN In-silico MOLECULAR DOCKING STUDY ON THE INTERACTION OF DIFFERENT PARABEN ESTERS (METHYL-, ETHYL-, PROPYL- AND BUTYL-PARABEN) WITH HUMAN THYROID HORMONE RECEPTOR α1 (THRα1) AND β1 (THRβ1)

Abstract

Thyroid hormones (THs) activate transcription of a large number of genes via binding with nuclear thyroid hormone receptors (THRs) that are either attached to the DNA genetic strands or located in proximity to them. However, the ever-increasing human anthropogenic activities have introduced numerous harmful chemicals in the environment, many of which share high degree of structural resemblance with the THs i.e., triiodothyronine (T3) and thyroxine (T4) and thus can interfere with the normal downstream receptor signalling. The present study used bioinformatics to perform a molecular docking analysis (Autodock 4.2.6) where different paraben esters (PBs) i.e., methyl- (MP), ethyl- (EP), propyl- (PP) and butyl- paraben (BP) were examined for their possible interaction with two human THR isoforms viz., THRα1 and THRβ1. Perceiving the free binding energies (ΔG) of different PB-THRs complexes, it has become evident that BP has the strongest binding interaction with both THRα1 (PDB Id- 1NAV) and THRβ1 (PDB Id- 1NAX) i.e., -6.51 and -6.14 kcal/mol respectively and also has highest number of amino acids interactions in the active sites, followed by PP, EP and MP. The co-crystal ligand exhibited binding energies of -10.43 and -10.52 kcal/mol for THRα1 and THRβ1 respectively. Therefore, the study firmly demonstrates that thyroid hormone receptor interaction of the selected PB esters rise with increase in length/complexity of the alkyl side chain. Given that all the investigated PB esters are capable binders of both the THRs, unremitting use of these chemical preservatives certainly could amend the receptor mediated signalling of THs.