Molecular Modelling Studies of Novel COX-2 Inhibitors

Abstract

Molecular modelling uses theoretical and computational chemistry, which offers insight into the nature of molecular systems. This chapter highlights the theoretical explanation of molecular modelling methods and describes the designing of novel tyrosine COX-2 inhibitors using molecular modelling as an example. As a first step, fragment-based drug design is used to design the novel tyrosine analogues and ligand-based drug design such as QSAR, and pharmacophore was used to identify the descriptors, ensemble of steric and electronic features, which is responsible for the selective COX-2 inhibition. The next step, structure-based drug design, was used to analyses intra- and intermolecular interactions in the drug receptor system to improve the binding affinity and pharmacokinetic properties. Finally, the pharmacokinetic and toxicity properties were predicted quantitatively using rationalization of observed structure-activity relationships and the results are reported.

Bioactivity of dihydropyrimidinone derivatives as inhibitors of cyclooxygenase-2 (COX-2): an in silico approach

“…30 Finally, the redocking of the original ligand was carried out on the receptor by the flexible docking method using the DOCK6 program. 31 The pose reproduction was considered successful if the redocking results show the same ligand pose as the original ligand before the docking process and have an RMSD value of ≤2.0 Å. 32 Then all the ligand candidates were docked to COX-2, and the selection of candidates for further analyses is based on the grid score and poses produced during the docking process.…”

Computational Approaches to Discover Novel Natural Compounds for SARS‐CoV‐2 Therapeutics

“…Additionally, the molecular docking studies elucidate on the probable binding modes of small molecules at the proteins binding pocket. For the current investigation, the CDOCKER programme accessible with the DS was employed [44–50] . The CDOCKER is a CHARMm‐based molecular dynamics (MD) method to dock ligands into a proteins binding site.…”