Preprint Article Version 1 This version is not peer-reviewed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)

How to cite: Perez, Y.R.; Alvarez, D..; Combariza, A. Ligand-Protein Interactions: A Hybrid ab initio/Molecular Mechanics Computational Study. Preprints 2019, 2019020124 (doi: 10.20944/preprints201902.0124.v1). Perez, Y.R.; Alvarez, D..; Combariza, A. Ligand-Protein Interactions: A Hybrid ab initio/Molecular Mechanics Computational Study. Preprints 2019, 2019020124 (doi: 10.20944/preprints201902.0124.v1).

Abstract

The enzymes Cyclooxygenase (COX) or prostaglandin-endoperoxide synthase (PTGS) are important in the synthesis of prostaglandins, which are the main mediating chemi- cals at inflammatory processes. The body produces two highly homologous COX isoforms, cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). COX-1 is involved in the pro- duction of prostaglandins which take part in physiological processes such as: protection of the gastric epithelium, maintenance of renal flow, platelet aggregation, neutrophil mi- gration and also expressed in the vascular endothelium; Meanwhile COX-2 is inducible by proinflammatory stimuli. To counteract the symptoms of inflammation, nowadays is very frequent the use of nonsteroidal antiinflammatory drugs (NSAIDs); These drugs in addi- tion to other benefits, can also cause side effects on people’s health (cardiovascular and respiratory problems, in the nervous system, among others). Due to the above, it is neces- sary to accelerate the investigations that allow to know in more detail the mechanisms of action that involve the use of natural plant products as pharmacological agents. In the pre- sent research, computational techniques are used, especially those based on the Molecular Docking Method to know the proteinligand interaction in systems of biological interest. It was possible to determine the structure-activity relationship in inflammatory processes involving the participation of a number of secondary plant metabolites such as luteolin, galangin, kaempferol, apigenin, morine and quercetin on the inactivation of the enzyme cyclooxygenase (COX-1 and COX -2). In the COX-1 / ligand coupling it was found that apigenin was the ligand which showed the lowest coupling energy with a value of -8.88, whereas quercetin showed the highest value (-6.65); for the coupling COX-2 / ligand the apigenin also showed the lowest energy value (-8.93), while kaempferol showed the highest value (-7.51). This shows that apigenin is the ligand with the best stability within the active site of both enzymes. On the other hand, quercetin showed the highest relative selectivity with a protein-ligand selectivity index (PLSI) of 1.17, while kaempferol showed an PLSI of 0.91. Taking into account the parameters of stability and selectivity we can say that of all the ligands used, quercetin would be the ideal to block COX-2.

Subject Areas

enzymes Cyclooxygenase, ligand, metabolites, antiinflammatory, Molecular Docking

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