Efficiency of Nitrification Inhibitor on Designing Nitrogen Fertilizer by Neem Compounds Based on Molecular Docking

Abstract

In the agricultural trade, nitrogen fertilizer is one among the popular fertilizers within the world market. However, the high use of nitrogen fertilizers causes negative impacts within the type of environmental pollution, each in water, soil, and within the air. Nitrification inhibitor required to enhance the potency of nitrogen fertilizer use to realize additional economical production of food crops and minimize fertilizer related pollution of the environment. Neem (Azadirachta indica) act as an inhibitor nitrification that contained high tannin and the other secondary metabolite compounds. Neem plants encapsulated by urea as a nitrification inhibitor can increase nitrogen efficiency in the soil during fertilization. This research is a computational experiment research in solving problems using Molecular Docking Analysis. Molecular Docking method was performed using AutoDock Vina Tools 1.5.6 and Open Babel 2.4.1 Program. The use of molecular docking aims to predict ligand bonds and target proteins that focus on affinity and bond interactions. The high and low affinity of ligand-protein bonds is influenced by free bond energies, surface interactions, and intermolecular interactions. The results represent Neem (A. Indica) contains high tannin and the other secondary metabolite compounds (Nimbin, Nimbidin, Nimbic Acid, Nimbidinin, Nimbinin, Azadirachtin, Diepoxy Azadiradione, Dyhidrogedunin, Gallic Acid and Gedunin). Those metabolite compounds can inhibiting 4 enzymes such as methane monooxygenase, Hydroxylamine oxidoreductase, Nitric oxide reductase and Nitrite Reductase. From 10 metabolite compounds, Diepoxy Azadiradione and Gedunin may become the most stable complex that indicated become strength binding energy based on the lowest energy score of −10.3 kcal/mol.
 HIGHLIGHTS
 
 One of the agricultural problem is the inefficiency of Nitrogen fertilization will be released in the form of N2O and Nitrate gases which pollute the environment as a result of the nitrification process
 Azadirachta indica is known to have secondary metabolite which have the ability to inhibit nitrification
 The molecular docking method was used as an initial analysis of the effectiveness of secondary metabolites from Azadirachta indica inhibiting enzymes that play a role in the nitrification process
 
 GRAPHICAL ABSTRACT

An In Silico Analysis of Synthetic and Natural Compounds as Inhibitors of Nitrous Oxide Reductase (N2OR) and Nitrite Reductase (NIR)

“…Thiocyanate (SCN − ) has been demonstrated to inhibit the reduction of nitrous oxide (N 2 O) produced for nitrate–nitrogen in growing cells of Paracoccus denitrificans [ 56 ]. Azadirachta indica (Neem) phytochemicals, namely azadirachtin, diepoxy azadiradione, dyhidrogedunin, gallic acid, gedunin, nimbin, nimbidin, nimbic acid, nimbidinin, and nimbinin, have been reported to dock with the nitric oxide reductase of Pseudomonas aeruginosa [ 57 ]. Among these phytochemicals, diepoxy azadiradione showed the least binding energy (−8.7 kcal/mol) with that of the Pseudomonas aeruginosa nitric oxide reductase (N 2 OR).…”

“…Nitrite reductase (NIR) has been reported from the following microorganisms: (i) Achromobacter cycloclastes , (ii) Alcaligenes faecalis , (iii) Alcaligenes sphaeroides , (iv) Bradyrhizobium japonicum , (v) Desulfovibrio desulfuricans , (vi) Escherichia coli , (vii) Fusarium oxysporum , (viii) Hyphomicrobium nitrativorans , (ix) Hyphomicrobium denitrificans , (x) Hyphomicrobium zavarzinii , (xi) Nitrosomonas europaea , (xii) Paracoccus denitrificans , (xiii) Pseudomonas aeruginosa , (xiv) Pseudomonas aureofaciens , (xv) Rhodopseudomonas sphaeroides , (xvi) Thiobacillus denitrificans , (xvii) Vibrio alginolyticus , (xviii) Vibrio fischeri , and (xix) Wolinella succinogenes [ 56 , 57 , 58 , 59 , 60 ]. Among these, Hyphomicrobium species are facultative methylotrophs, commonly found in water and soil and also isolated from sewage treatment plants [ 59 ].…”

“…In the present study, six ligands, namely 3,4-dimethyl pyrazole phosphate, 5-iodonaphthyl-1-azide, methyl azide, nicotinoylazide, 2-nitrophenyl azide, and thiocyanate, were found to interact with the Leu421 amino acid (A.A) residue of Hyphomicrobium denitrificans nitrite reductase (NIR), as shown in Table 5 . Ten phytochemicals of neem ( Azadirachta indica ), such as azadirachtin, diepoxy azadiradione, dyhidrogedunin, gallic acid, gedunin, nimbin, nimbidin, nimbic acid, nimbidinin, and nimbinin were demonstrated to bind with that of the Paracoccus pantotrophus cytochrome CD1 nitrite reductase [ 57 ]. Among these phytochemicals, both the nimbidin and nimbidinin showed the least binding energy (−8.3 kcal/mol) with that of the Paracoccus pantotrophus cytochrome CD1 nitrite reductase (NIR).…”

Computational Exploration of Berberis lycium Royle: A Hidden Treasure Trove for Antiviral Development

“…The top phytochemicals identified by the binding energy values in the AutoDock 1.5.6 program were taken into consideration based on their binding location and probable interactions with the major residues. 73 , 74 The conformations with the lowest connection affinities (less than –7.0 kcal/mol) were chosen as best after the docking procedure to further monitor interacting residues ( Figures 2 - 4 ). Punjabine has shown the strongest binding affinity with NS2BNS3 (–10.9 kcal/mol), NS5 (–10.3 kcal/mol), and influenza RdRP (–10.4 kcal/mol).…”

Molecular Recognition ofMoringa oleiferaActive Compounds for Stunted Growth Prevention Using Network Pharmacology and Molecular Modeling Approach

“…oleifera at the catalytic site of the protein target, molecular docking is carried out. This method is extensively used to construct a new drug because it can find the orientation pose of a particular small molecule in binding with a receptor. − To assess the stability of a molecular docked ligand–receptor complex, we perform all-atom molecular dynamics (MD) and estimate validation metrics such as root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), radius of gyration ( R g ), solvent-accessible surface area (SASA), and hydrogen bonds. Moreover, the thermodynamic quantities of the constructed complex are estimated from the collected trajectories of the MD simulation.…”