Exploring the Energetics and Intermolecular Interactions of Myoglobin Inhibiting Drugs: Bioinformatics

Abstract

Introduction: Docking techniques were employed to ascertain the nature of interaction existing between Myoglobin (Mb) with drugs that specifically inhibit Mb.

Objectives: Mb as the host and the guest molecules comprises drugs belonging to family of antibiotics (Amoxicillin (AMX), Penicillin G (PenG)), antipyretics (Aspirin (ASA)) and antipsychotics (Promazine (PRZ), Chlorpromazine (CPZ)). 4-dicyanomethylene-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran (DCSP) dye as the competing guest was simultaneously docked to protein-drug complex to explore the binding affinity of protein-drug vs protein-dye complex. The drugs chosen were based on the specific inhibiting action on Mb wherein the protein acts as the host molecule and drug as the guest.

 Methods: Molecular Docking (Mol.Dock) studies by AutoDock software version 4.2 as performed for regarding protein- drug-dye system of 10 conformers generated, the stable clusters were selected in the descending order of binding energy (B.E) Mb-drug complex was further docked with DCDAP dye based on Lipinski rule of Five.

Results: The binding energy (B.E) of Mb-drug complex were in the order of AMX > PenG > CPZ > PRZ > ASA. The introduction DCSP dye with the Mb-drug complex resulted in enhanced binding stability. However, simultaneous docking of these drugs to Mb-dye complex resulted in a comprehensive decrease in the affinity of dye towards Mb. The stability and the binding affinity of host-guest complex in the presence of competing guest and vice versa were explored in depth wherein the bimolecular interactions play a significant role.

Conclusions: The study highlight’s the importance of Mol.Dock in understanding the biochemical interactions existing between Mb with drugs and dye, providing a significant and valuable link between chemistry and medicine. Both polar and non-polar amino acids contribute to the stability of the complexes in varying aspects.