Steriochemistry and validation of the structure of cyclooxygenase, preferred target of controversial non-steroidal anti-inflammatory drugs during the COVID 19 pandemic
Keywords:Steriochemistry, validation, cyclooxygenase, non-steroidal anti-inflammatory drugs, COVID 19
During COVID-19 infection, the scarce published data on nonsteroidal anti-inflammatory drugs is very controversial. In the literature, several models of cyclooxygenase, their preferred target, have been identified. The aim is to study their sterochemistry and validate the best structure. PDB entries were viewed using Discovery Studio 2.5 software. MolProbity was used for steriochemical analysis. The structures of COX bound to Naproxen (3NT1: 1.73 Å) and Ibuprofen (4PH9: 1.81Å) are of higher resolution. In the Ramachandran diagram, for 4PHP and 3LN1, 100.0% of the residues were in allowed regions. For the Rlibre factor the values of (19.8%) for 4PH9, (20.0%) for 3NT1 and (22.4%) for 1CVU were within the expected ranges. They were rather high for 3LN1, 1PXX and 4COX. The clashscores for 3NT1 (99th percentile) and 4PH9 (98th percentile) were at the top of the best ranges. 4PH9 (sidechain outliers: 1.5%) and 3NT1 (sidechain outliers: 1.8%) were modeled with their preferred rotamers. By comparing all metrics, 4PH9 appears to be the finest crystal structure. PDB entries do not necessarily constitute a reliable source of steriochemistry. Our study made it possible to verify the adherence of the models to the structural principles established to guarantee their quality. This is an essential step in the design of structure-based drugs.
Keywords: Steriochemistry, validation, cyclooxygenase, non-steroidal anti-inflammatory drugs, COVID 19