Pesticides environmental pollutants (PEPs) are environmental contaminants with significant taxological risk factor that varies with their chronic and acute exposure and include cellular poisoning, DNA damage and cancer risk. World health organization categorizes PEPs on the basis of their lethal dose (LD50) and of these, aldicarb-sulfoxide, methamidophos, fenpropathrin, and carbofuran, although vary in molecular sizes and structural complexity, are extremely/highly hazardous PEPs (LD50 &lt; 50 mg/kg). Therefore, there is a need to fundamentally investigate the interaction of PEPs with biologically relevant macromolecules. The first aspect of this in silico study involves molecular docking and molecular dynamics (MD) simulation study to probe the interaction of selected PEPs with a promiscuous and the dominant serum protein, human serum albumin (HSA). HSA is a 66 kDa, multidomain, monomeric protein and is unique in its ability to bind various endogenous and exogenous molecules on its one of the several binding sites. Our molecular docking and MD simulation study investigates PEPs binding preference for one subdomain vs the other subdomain of HSA and specifically explores key structural determinants of ligand and protein that direct preferential binding for one ligand vs the other and one binding site vs the other. The second aspect of this study involves investigating the PEPs binding to human drug metabolizing cytochrome P450 enzymes, CYP3A4, CYP2D6 and CYP2C9. These three P450s metabolize &gt; 50% exogeneous molecules in the liver. Therefore, potential binding and subsequent inhibition/activation of these P450s by exogeneous molecules have severe consequences for human health. Using molecular docking, we have specifically investigated binding of PEPs with these P450s and determined whether this binding could lead to PEPs metabolism and/or P450 activation or inhibition. The results of this study reveal structural characteristics of PEPs, and HSA and P450s that contribute to their interaction leading to PEPs poisoning.

In silico study of pesticides environmental pollutants interaction to human serum albumin and human cytochrome P450 enzymes

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.