Multi spectroscopy and molecular modeling aspects related to drug interaction of aspirin with alpha chymotrypsin; structural change and protease activity

Abstract

Examining the structure of enzymes versus drugs can help us understand the effects of a drug or its side effects. In this study, we investigated the effect of Aspirin (N-Acetyl salicylic acid or NAS) on alpha chymotrypsin (α-Chy). NAS is a non-steroidal drug, that dose anti-inflammatory action by inactivating cyclooxygenase enzymes. It is also prescribed in medicine to treat fever and inflammation caused by wounds. α-Chy is a powerful secretory protease from the pancreas. In the study of Uv–Vis, the effect of different concentrations of NAS on α-Chy, NAS was able to increase absorption intensity of α-Chy. This is due the effect of NAS on the 3D structure of the α-Chy. In the fluorescence emission spectrum study, NAS caused the α-Chy emission to be quenched. Also, the type of perusal was considered static. Calculation of thermodynamic parameters showed that this reaction was performed spontaneously. The type of bond between NAS and α-Chy was hydrophobic forces. The kinetic reaction comes from the way of α-Chy activity illustrated that NAS acts as an activator. Other techniques performed included investigating the thermal stability of the enzyme (TM) in the presence of ligand. The melting temperature of α-Chy decreased in the presence of NAS, TM, and the enzyme became more unstable. Also, in the secondary structure study for α-Chy, in the complex with NAS, the alpha-helix value increased, indicating that the enzyme was partially open, as shown by the simulation and Tm results. This information suggests that NAS can activate and destabilize this enzyme by entering the gastrointestinal tract.