Designing, docking and molecular dynamics simulation studies of novel cloperastine analogues as anti-allergic agents: homology modeling and active site prediction for the human histamine H1 receptor

Abstract

The present study predicts a three-dimensional model for the histamine H1 receptor and the design of antihistamine inhibitors using cloperastine as the core molecule by docking studies. In this work, we predicted a three-dimensional structure of the histamine H1 receptor using the MODELLER9V7 software. The protein structure was developed based on the crystal structure of the histamine H1 receptor, the lysozyme chimera of Escherichia virus T4 (PDB ID: 3RZE_A) target collected from the PDB data bank. Using molecular dynamics simulation methods, the final predicted structure is obtained and further analyzed by VERIFY3D and PROCHECK programs, confirming that the final model is reliable. The drug derivatives of cloperastine were designed and docking was performed with the designed ligands along with the drug. The predicted model of the histamine H1 receptor structure is stable and confirms that it is a reliable structure for docking studies. The results indicate that MET 183, THR 184 and ILE 187 in the histamine H1 receptor are important determinant residues for binding as they have strong hydrogen bonding with cloperastine derivatives. The drug derivatives were docked to the histamine H1 receptor protein by hydrogen bonding interactions and these interactions played an important role in the binding studies. The molecule 1-{2-[(4-chlorophenyl) (phenyl) methoxy] ethyl}-4-methylenepiperidine showed the best docking results with the histamine H1 receptor. The docking results predicted the best compounds, which may act as better drugs than cloperastine and in the future, these may be developed for anti-allergy therapy.