Preprint Article Version 2 Preserved in Portico This version is not peer-reviewed

Ligand-Protein Interactions: A Hybrid ab initio/Molecular Mechanics Computational Study

Version 1 : Received: 11 February 2019 / Approved: 13 February 2019 / Online: 13 February 2019 (16:27:04 CET)
Version 2 : Received: 28 February 2019 / Approved: 1 March 2019 / Online: 1 March 2019 (12:57:24 CET)
Version 3 : Received: 6 March 2019 / Approved: 7 March 2019 / Online: 7 March 2019 (14:09:04 CET)
Version 4 : Received: 23 May 2019 / Approved: 29 May 2019 / Online: 29 May 2019 (11:39:02 CEST)

How to cite: Perez, Y.R.; Alvarez, D.; Combariza, A. Ligand-Protein Interactions: A Hybrid ab initio/Molecular Mechanics Computational Study. Preprints 2019, 2019020124. Perez, Y.R.; Alvarez, D.; Combariza, A. Ligand-Protein Interactions: A Hybrid ab initio/Molecular Mechanics Computational Study. Preprints 2019, 2019020124.


Cyclooxygenases (COX), or prostaglandin endoperoxide synthases (PTGS), are key enzimes in the synthesis of prostaglandins, which are chemical species critical in mediating inflammatory processes. There are two highly homologous COX isoforms: COX-1 and COX-2. COX-1 is involved in the production of prostaglandins, chemical compuounds that take part in physiological processes such as: protection of the gastric epithelium, maintenance of renal flow, platelet aggregation, neutrophil migration and, also, are expressed in the vascular endothelium. Meanwhile, COX-2 is induced by proinflammatory stimuli. It is very frequent the use of nonsteroidal antiinflammatory drugs (NSAIDs) to counteract the symptoms of inflammatory processes. These drugs, in addition to its benefits, can cause side effects on people’s health, such as cardiovascular and respiratory problems, among others. In the past years, it has been recognized the potential of plants secondary metabolites as pharmacological agents, prompting the need for investigations that shed light into its mechanism of action. In this work we have applied computational techniques, based on quantum chemistry and mechanical statistics, to study the protein-ligand interaction involving COX’s and secondary metabolites from natural sources. Our aim is to determine the structure activity interplay in processes involving the participation of secondary plant metabolites such as luteolin, galangin, kaempferol, apigenin, morine and quercetin on the inactivation of COX’s. From molecular docking analysis, we have extracted the energetics of the COX-(1,2)/metabolite coupling. By defining energy based factors, we have determined a procedure that predicts the chemical species with highest stability and selectivity towards inactivation of COX-2 over COX-1. The results are discussed with regard to conformational features of the selected ligands and its intermolecular strong/weak interactions inside the active-sites of the COX’s hosts.


enzymes Cyclooxygenase, ligand, metabolites, antiinflammatory, Molecular Docking


Biology and Life Sciences, Biochemistry and Molecular Biology

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Metrics 0

Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.