Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed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.


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.


enzymes Cyclooxygenase, ligand, metabolites, antiinflammatory, Molecular Docking


Biology and Life Sciences, Biochemistry and Molecular Biology

Comments (0)

Comment 1
Received: 13 February 2019
Commenter: Dinais Álvarez
The commenter has declared there is no conflict of interests.
Comment: Conclusions

The interactions of the flavonoids with the amino acids of the active sites of the enzymes, are produced through the hydroxyl groups present in the structure. The numbers of -OH vary according to the type of flavonoid, but it is important to mention that one flavonoid is not more stable or selective than another because it has more -OH groups.
On the other hand, hydrogen bonds do not define the stability of the ligands throughout the coupling process, that is, a metabolite that forms more hydrogen bonds than another metabolite, is not guaranteed to be more stable.
According to the

Considering the above, we must emphasize that both the stability index and the selectivity index are independent parameters, hat is, the fact that a metabolite is stable in the active site of a COX does not mean that it is selective in the same active site. For example, Apigenin shows a high stability index but a low selectiviy index.
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