The interaction analysis between human serum albumin with chlorpyrifos and its derivatives through sub-atomic docking and molecular dynamics simulation techniques.

Unlabelled: Chlorpyrifos (CPF) is an extensively used organophosphate pesticide for crop protection. However, there are concerns about it contaminating the environment and human health, with estimated three lakh deaths annually. The molecular modeling protocol was assisted in redesigning thirteen well-known CPF linkers and inserting them at five selectable CPF (R1-R5) positions of CPF to get 258 CPF derivatives. CPF and its derivatives were optimized using LigPrep and docked to a grid centralized on Trp214 using extra precision glide docking. The Binding free energy of complexes was calculated using molecular mechanics/generalized born surface area (MM-GBSA). CPF and CPFD-225 have glide scores of - 3.08 and - 6.152 kcal/mol, respectively, with human serum albumin and ΔG bind for CPF (- 33.041817 kcal/mol) (- 52.825 kcal/mol) for CPF-D225. The top ten CPF derivatives showed at least ninefold better binding free energy than the CPF proposed for polyclonal antibody production. Subsequently, molecular docking studies revealed that CPF and its derivatives could bind to human serum albumin (HSA). Furthermore, using the Desmond package, a 100-ns molecular dynamics (MD) simulation was performed on the potential binding site. The final systems of CPF-HSA and CPF-222D complexes consist of 76,014 and 76,026 atoms, respectively. The physical stability of both the systems (CPF-HSA and CPF-222D) was analyzed by considering the overall potential energy, RMSF, RMSD, Hydrophobic interactions, and water-mediated patterns, which showed total energy of - 141,610 kcal/mol and - 140,150 kcal/mol, respectively.

Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03344-7.