SA score for all the molecules involved in the study.

<p>SA score for all the molecules involved in the study.</p

Molecular dynamics simulation of COX-2-C_773 complex.

<p>(A) RMSD trajectory of the protein backbone in reference to the structure obtained subsequent to docking. (B) Superimposition of the complex before and after simulation run. (C) Molecular interactions between the two partners. Hydrogen bond forming residues are shown in green and hydrophobically interacting residues are shown in blue.</p

Eleven drug molecules developed against COX-2 which were used for the generation of seed structures in LigBuilder.

<p>Eleven drug molecules developed against COX-2 which were used for the generation of seed structures in LigBuilder.</p

Molecular interaction pattern between ligand and protein after docking.

<p>(A) Interactions between COX-2 and C_773. (B) Interactions between COX-2 and C_997. Hydrogen bond forming residues are shown in green and hydrophobically interacting residues are shown in blue.</p

Modelled structure of COX-1 and COX-2.

<p><b>Comparison of modelled structures with their template structures revealed the active sites of located in the enzymes.</b> (A) Membrane binding domain, epidermal growth factor binding domain, peroxidase active site, and cyclooxygenase active site of modeled COX-1 and COX-2 enzymes. Shape of cyclooxygenase active sites are shown in yellow and four helices of membrane binding domains are located just beneath it, represented in red. A heme group was present at the peroxidase active site of COX-2 enzyme. (B) Flurbiprofen (brown) was inherited at the cyclooxygenase active site of COX-1 modelled structure from its template structure (PDB ID: 1CQE). Area of active site is depicted by the use of white dots, yellow mesh surface shows hydrophobic region and green mesh surface shows hydrophilic region of the active site. (C) Diclofenac (cyan) was inherited at the cyclooxygenase active site of COX-2 modelled structure from its template structure (PDB ID: 1PXX). Same colours were used to show the area of active site, hydrophobic region and hydrophilic region of the active site. Green hydrophilic channel in COX-2 was larger than the channel of COX-1 enzyme.</p

Computational Structure-Based <i>De Novo</i> Design of Hypothetical Inhibitors against the Anti- Inflammatory Target COX-2

<div><p>Cyclooxygenase-2 (COX-2) produces prostaglandins in inflamed tissues and hence has been considered as an important target for the development of anti-inflammatory drugs since long. Administration of traditional non-steroidal anti-inflammatory drugs (NSAIDs) and other COX-2 selective inhibitors (COXIBS) for the treat of inflammation has been found to be associated with side effects, which mainly includes gastro-intestinal (GI) toxicity. The present study involves developing a virtual library of novel molecules with high druglikeliness using structure-based <i>de novo</i> drug designing and 2D fingerprinting approach. A library of 2657 drug like molecules was generated. 2D fingerprinting based screening of the designed library gave a unique set of compounds. Molecular docking approach was then used to identify two compounds highly specific for COX-2 isoform. Molecular dynamics simulations of protein-ligand complexes revealed that the candidate ligands were dynamically stable within the cyclooxygenase binding site of COX-2. The ligands were further analyzed for their druglikeliness, ADMET properties and synthetic accessibility using knowledge based set of rules. The results revealed that the molecules are predicted to selectively bind to COX-2 enzyme thereby potentially overcoming the limitations posed by the drugs in clinical use.</p></div

Molecular dynamics simulation of COX-2-C_997 complex.

<p>(A) RMSD trajectory of the protein backbone in reference to the structure obtained subsequent to docking. (B) Superimposition of the complex before and after simulation run. (C) Molecular interactions between the two partners. Hydrogen bond forming residues are shown in green and hydrophobically interacting residues are shown in blue.</p