An in silico Approach Towards Crop Improvement by ACC Synthase Inhibition Declining Ethylene Production

2017 ◽  
Vol 13 (1) ◽  
pp. 11-19
Author(s):  
Jasarat Ali ◽  
Rupesh K. Mishra ◽  
Chhedi L. Gupta ◽  
Dinesh C. Sharma ◽  
Preeti Bajpai ◽  
...  
Keyword(s):  
Binding Energy ◽  
Organic Contaminants ◽  
In Silico ◽  
Growth Promotion ◽  
Crop Improvement ◽  
3D Structure ◽  
Acc Synthase ◽  
Docking Study ◽  
Primary Objective ◽  
Hydrogen Bond Interaction

Introduction: The increased level of ethylene inhibits root elongation and causes physiological damage, thereby reduces ethylene level imparts a positive support against various biotic and abiotic stresses viz. phytopathogens, extreme temperatures, hyper salinity, flooding, drought, metal/organic contaminants and insect predation. The metabolic pathways showed the involvement of ACC synthase inhibition for ethylene suppression in plants. Objective: The primary objective of this study focused towards the use of In-silico approach to assess the inhibitory effect of S-adenosyl methionine (SAM) analogue on ACC synthase activity. Methods: The 3D structure of ACC synthase of Pisum sativum was constructed using modeler 9v11 software. The reliability of developed model was evaluated by PROCHECK, ERRAT and ProSA web servers. Furthermore the molecular interactions between substrate SAM and inhibitors were performed. Result: The docking study demonstrated that the binding energy of the substrate SAM is -5.37 Kcal/mol. The SAM analogue (Inhibitors) considered in this study were 3-dzSAHC, SAHC, sinefungin, SIBA, 7-dz-SIBA, 1-dz-SIBA,3-dz-SIBA and S-n-Butyladenosine. Among these analogues, 7-dz-SIBA was found to be most effective on ACC synthase as inhibitor due to lowest binding energy (- 5.51Kcal/mol) and strong Ki value (91.74M). The LYS276 amino acid residue of ACC synthase was observed in the interaction with both substrates SAM and 7-dz-SIBA (S-isobutyl-7-deazaadenosine) demonstrates as most crucial catalytic residue for molecular interaction. Conclusion: This study successfully screened most potent inhibitor for ACC synthase which have indicated the compounds 7-dz- SIBA as effective inhibitor with lowest binding energy, better hydrogen bond interaction and strong inhibition constant compared to others compounds studied. Thus 7-dz-SIBA can be projected to use as a growth enhancer for overall crop improvement. It may help in plant growth promotion, prevents the plants from various environmental stress and phytopathogenic infections etc.

scholarly journals ANTI-PARKINSON POTENTIAL OF PERSEA AMERICANA SEED EXTRACTS THROUGH IN-SILICO DOCKING STUDY

2020 ◽  
pp. 152-155
Author(s):  
RACHAEL EVANGELINE ◽  
NIHAL AHMED
Keyword(s):  
Binding Energy ◽  
Hydrogen Bonds ◽  
In Silico ◽  
Water Extract ◽  
Docking Study ◽  
Persea Americana ◽  
Ligand Docking ◽  
Docking Analysis ◽  
In Silico Docking ◽  
Free Binding Energy

Objective: The aim of this study is to investigate the potential of Persea americana extracts for their Anti-Parkinson application through an in-silico docking study. Methods: PubChem and protein data bank databases were used to retrieve 3D structures. AutoDock4 was used to perform protein-ligand docking analysis. PyMOL was used to visualize the docking results. Results: Among the 30 ligand, the highest affinity was demonstrated by Hesperidin with a free binding energy of −6.8 kcal/mol and formation of five hydrogen bonds. The second highest significance was demonstrated by Biphenyl 4-(4-diethylaminobenzylidenamino) with a free binding energy of −5.9 kcal/mol with the formation of 2 hydrogen bonds. Among the three sets of phytochemicals from different solvent extracts, water extract demonstrated the highest potential as Anti-Parkinson active. Conclusion: P. americana extracts were analyzed for their Anti-Parkinson potential, and among the three extracts, the aqueous extract was predicted to have significant Anti-Parkinson potential, based on in silico docking analysis, due to the presence of active phytochemicals such as Hesperidin and others.

scholarly journals In silico docking analysis of selective bioactive compounds of Phyllanthus acidusaqueousfruit extractagainst MAPK1

Biomedicine ◽  
2021 ◽  
Vol 41 (2) ◽  
pp. 349-357
Author(s):  
E. Padmini ◽  
M. Kavitha
Keyword(s):  
Binding Energy ◽  
Cell Survival ◽  
Bioactive Compounds ◽  
In Silico ◽  
Docking Study ◽  
Mitogen Activated Protein Kinase ◽  
Molecular Docking Study ◽  
Ligand Complex ◽  
In Silico Docking ◽  
Methyl Prednisolone

Introduction and Aim: Phyllanthus acidus L.Skeels (Family: Phyllanthaceae) or Star Gooseberry which bears small, edible, juicy, sour, yellow berries fruit is known as a “liver tonic” in ayurvedic medicine. However, the behavior of the plant fruit or its constituents in cell apoptosis/cell survival is unknown. Hence, the purpose of thepresent study was to perform an in silico docking of selective bioactive compounds of aqueous extract of fruit of P.acidus (PAFAE) against MAPK1. Mitogen activated protein kinase is a family of serine threonine specific protein kinases- MAPK1/ERK1/2, JNK1-3, p38MAPK and ERK5.Activation ofMAPK1 promotes cell survival in certain tissues by inhibiting proapoptotic proteins and by stimulating anti apoptotic factors.   Methodology: In silico docking studies was carried out using bioinformatics tools.The active compounds (Trihomovitamin D3; 2Z,6Z,8Z,12E Hexadecatetraenoic acid, Methyl prednisolone, Hydroxysalmeterol and Tridesacetoxykhivorin) ofP.acidus aqueous fruit extract were docked against MAPK1 resulting in receptor-ligand complex.   Results: The binding energy is correlated with the probability of affinity and stable bound between ligand and its receptor.   Conclusion: The molecular docking study of selective bioactive compounds of PAFAE with MAPK1 protein revealed that Tridesacetoxykhivorinand Methyl Prednisolone, is having good interaction in favorable pose with MAPK1 as shownfrom theireffective binding energy(-7.79kcal/mol and -7.19 kcal/mol), strong bond length and interactions with active site of MAPK1.

scholarly journals In silico Study of Potential Non-oxime Reactivator for Sarin-inhibited Human Acetylcholinesterase

2021 ◽  
Vol 29 (3) ◽  
Author(s):  
Rauda A. Mohamed ◽  
Keat Khim Ong ◽  
Norhana Abdul Halim ◽  
Noor Azilah Mohd Kasim ◽  
Siti Aminah Mohd Noor ◽  
...  
Keyword(s):  
Binding Energy ◽  
In Silico ◽  
Docking Study ◽  
Dynamics Simulation ◽  
Nucleophilic Attack ◽  
Organophosphate Poisoning ◽  
Nipecotic Acid ◽  
Computational Screening ◽  
The Stability ◽  
New Compounds

The search for new compounds other than oxime as potential reactivator that is effective upon organophosphate poisoning treatments is desired. The less efficacy of oxime treatment has been the core factor. Fourteen compounds have been screened via in silico approach for their potential as sarin-inhibited human acetylcholinesterase poisoning antidotes. The selection of the compounds to be synthesized based on this computational screening, reduces the time and cost needed. To perform the docking study of sarin-inhibited acetylcholinesterase and reactivator-sarin inhibited acetylcholinesterase complexations, a bioinformatics tool was used. Estimation of the nucleophilic attack distance and binding energy of fourteen potential compounds with sarin inhibited acetylcholinesterase complexes to determine their antidote capacities was carried out using Autodock. A commercially available antidote, 2-PAM was used for the comparison. The best docked-pose was further examined with molecular dynamics simulation. Apart from being lipophilic, a compound with a carboxylic acid, (R)-Boc-nipecotic acid is shown to exhibit 6.29 kcal/mol binding energy with 8.778 Å distance of nucleophilic attack. The stability and flexibility of the sarin-inhibited acetylcholinesterase, complexed with (R)-Boc-nipecotic acid suggests this compound should be tested experimentally as a new, promising antidote for sarin-inhibited acetylcholinesterase poisoning.

De novo Design and in-silico Studies of Coumarin Derivatives as Inhibitors of Cyclin Dependent Kinase-2

2017 ◽  
Vol 4 (4) ◽  
pp. 46-56
Author(s):  
Ashok Sharma ◽  
Badvel Pallavi ◽  
Riddhidev Banerjee ◽  
Mariasoosai Ramya Chandar Charles ◽  
Mohane Selvaraj Coumar ◽  
...  
Keyword(s):  
Binding Energy ◽  
In Silico ◽  
De Novo ◽  
Docking Study ◽  
Binding Mode ◽  
Coumarin Derivatives ◽  
Standard Drug ◽  
Lipinski’S Rule ◽  
In Silico Studies ◽  
Binding Cavity

In the present study, around sixty-two novel coumarin derivatives were designed as CDK-2 inhibitors based on essential pharmacophoric requirements. All the designed compounds were subjected to docking study using AutoDock 4.2 against CDK-2 protein (PDB ID: 1HCK). Molinspiration and Osiris property explorer were used to predict Lipinski’s rule of five and toxicity profile. The Structure Activity Relationship study revealed that, the substitution at R1 and R4 of coumarin nucleus enhances the binding energy and inhibitory constant values from nanomolar to picomolar range. Among the designed analogues, compound 15, 28, 43 and 59 showed significant binding energy and inhibitory constant values as compared to the standard drug Olomoucine and Deschloroflavopiridol. Most of the designed analogues showed similar binding mode and orientation inside the active site of the protein as that of the standard drug, which strongly indicates that the designed molecules may emerge as potent inhibitors of CDK-2. Next, molecular dynamics study of the significantly active molecule 15 was studied for 10 ns, in order to determine the stability of the coumarin molecules inside the binding cavity of the protein. In-silico investigations suggest that the de novo designed coumarin derivatives were potentially in-silico bioactive and need to be synthesized and tested further.

Identification of Adjacent NNRTI Binding Pocket in Multi-mutated HIV1- RT Enzyme Model: An in silico Study

2018 ◽  
Vol 16 (2) ◽  
pp. 121-129 ◽  
Author(s):  
R.F. Kamil ◽  
U. Debnath ◽  
S. Verma ◽  
Y.S. Prabhakar
Keyword(s):  
In Silico ◽  
Point Mutations ◽  
Homology Model ◽  
Docking Study ◽  
Binding Pocket ◽  
Docking Studies ◽  
Primary Objective ◽  
Multiple Point ◽  
Enzyme Model ◽  
Hiv 1

Introduction: A possible strategy to combat mutant strains is to have a thorough structural evaluation before and after mutations to identify the diversity in the non-nucleoside inhibitor binding pocket and their effects on enzyme-ligand interactions to generate novel NNRTI’s accordingly. Objective: The primary objective of this study was to find effects of multiple point mutations on NNRTI binding pocket. This study included the contribution of each individual mutation in NNIBP that propose an adjacent binding pocket which can be used to discover novel NNRTI derivatives. Methods: An in Silico model of HIV-1 RT enzyme with multiple mutations K103N, Y181C and Y188L was developed and evaluated. Two designed NNRTI pyridinone derivatives were selected as ligands for docking studies with the homology model through alignment based docking and residue based docking approaches. Binding pockets of wild type HIV-1 RT and multi-mutated homology model were compared thoroughly. Result and Discussion: K103N mutation narrowed the entrance of NNRTI binding pocket and forbade electrostatic interaction with α amino group of LYS103. Mutations Y181C and Y188L prevented NNRTI binding by eliminating aromatic π interactions offered by tyrosine rings. Docking study against new homology model suggested an adjacent binding pocket with combination of residues in palm and connection domains. This pocket is approximately 14.46Å away from conventional NNRTI binding site. Conclusion: Increased rigidity, steric hindrance and losses of important interactions cumulatively prompt ligands to adapt adjacent NNRTI binding pocket. The proposed new and adjacent binding pocket is identified by this study which can further be evaluated to generate novel derivatives.

scholarly journals Targeting CoV-2 Spike RBD and ACE-2 Interaction with Flavonoids of Anatolian Propolis byin silicoandin vitroStudies in terms of possible COVID-19 therapeutics

2021 ◽  
Author(s):  
Halil Ibrahim Guler ◽  
Fulya Ay Sal ◽  
Zehra Can ◽  
Yakup Kara ◽  
Oktay Yildiz ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Caffeic Acid ◽  
In Silico ◽  
Docking Study ◽  
Caffeic Acid Phenethyl Ester ◽  
Elisa Test ◽  
Molecular Docking Study ◽  
Inhibitory Potential

ABSTRACTPropolis is a multi-functional bee product with a rich in polyphenols. In this study, the inhibition effect of Anatolian propolis against SARS coronavirus-2 (SARS CoV-2) was investigated asin vitroandin silico. Raw and commercial of propolis samples were used in the study and it was found that both of were rich in caffeic acid, p-coumaric acid, ferulic acid, t-cinnamic acid, hesperetin, chrysin, pinocembrin and caffeic acid phenethyl ester (CAPE) by HPLC-UV analysis. The ethanolic propolis extracts (EPE) were used in the screening ELISA test against the spike S1 protein (SARS Cov-2): ACE-2 inhibition KIT forin vitrostudy. Binding energy constants of these polyphenols to the CoV-2 Spike S1 RBD and ACE-2proteinwere calculated separately as molecular docking study using AutoDock 4.2 molecular docking software. In addition, pharmacokinetics and drug-likeness properties of these eight polyphenols were calculated according to the SwissADME tool. Binding energy constant of pinocembrin was the highest for both of the receptors, followed by chrysin, CAPE and hesperetin.In silicoADME behavior of the eight polyphenols were found potential ability to work effectively as novel drugs. The findings of both studies showed that propolis has a high inhibitory potential against Covid-19 virus. However, further studies are needed.

scholarly journals DESIGN AND SCREENING OF GALLIC ACID DERIVATIVES AS INHIBITORS OF MALARIAL DIHYDROFOLATE REDUCTASE (DHFR) BY IN SILICO DOCKING

2017 ◽  
Vol 10 (2) ◽  
pp. 330 ◽  
Author(s):  
Ade Arsianti Arsianti ◽  
Hendri Astuty ◽  
Fadilah Fadilah ◽  
Anton Bahtiar ◽  
Hiroki Tanimoto ◽  
...  
Keyword(s):  
Gallic Acid ◽  
Dihydrofolate Reductase ◽  
In Silico ◽  
3D Structure ◽  
Geometry Optimization ◽  
Docking Study ◽  
Open Chain ◽  
In Silico Docking ◽  
High Prevalence ◽  
Infection Disease

Objective: Malaria is an infection disease caused by plasmodium parasite with high prevalence in tropic and subtropic countries. The aim of this work was to design and screening of  gallic acid derivatives as inhibitors of malarial dihydrofolate reductase (DHFR) by in silico docking.Methods: The derivatives were designed by expanding the carboxyl group of gallic acid with open-chain moiety of L-threonine-allyl esters, as well as to modify the hydroxy groups on the aromatic ring of gallic acid with methoxyl group in the derivatives.  In silico approach has been utilized in finding the potential antimalaria of gallic acid derivatives. Fourteen Gallic acid derivatives (compound 2-15) were modeled into 3D structures by  ACD Labs software. Geometry optimization and minimization of energy 3D structure of gallic acid derivatives as ligands using the MOE software.  Docking process and amino acid analysis were executed by using MOE software. Results: In silico docking study resulted in the three top-ranked compounds, namely compound 5, 8 and 12. Among those three top-ranked compounds, compound 12 (octyl gallate), exhibited the strongest interaction and greatest inhibitory activity against the receptor of malarial DHFR.Conclusion Our results clearly demonstrated that compound 12 (octyl gallate) could be developed as a promising candidate for  the new anti-malarial agent.   

scholarly journals ANTI-METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS POTENTIAL OF PHYTOCHEMICALS IN TERMINALIA CATAPPA AND THEIR PROPOSED IN SILICO MECHANISM OF ACTION

2019 ◽  
pp. 133-137
Author(s):  
LOKESH RAVI ◽  
DIVYA JINDAM ◽  
SUGANYA KUMARESAN ◽  
VENKATESH SELVARAJ ◽  
JAYARAMA REDDY
Keyword(s):  
Staphylococcus Aureus ◽  
Binding Energy ◽  
Hydrogen Bonds ◽  
Mechanism Of Action ◽  
In Silico ◽  
Ethanol Extract ◽  
Docking Study ◽  
Ligand Docking ◽  
Methicillin Resistant ◽  
Antibacterial Potential

Objective: The objective of this study was to investigate the antibacterial potential of leaves of this Terminalia catappa and identify the mechanism of action for those phytochemicals present in this leaves. Methods: Phytochemicals were extracted using maceration and the extracts were analyzed using gas chromatography–mass spectrometry (GC-MS) to identify the chemical structure. Antibacterial potential was evaluated using agar well diffusion. The phytochemicals were subjected to in silico protein–ligand docking study to identify the mechanism of action. Results: In vitro antibacterial study demonstrated that the ethanol extract of the leaves has significant antibacterial activity against Staphylococcus aureus (SA) and methicillin-resistant SA (MRSA) with a zone of inhibition of 16 mm and 18 mm, respectively, at a concentration of 2 mg/ml. The chloroform and hexane extracts of the leaves did not demonstrate any significant activity. Based on GC-MS analysis and literature review, 12 phytochemicals were identified to be present in the ethanol extract of the T. catappa leaves. These molecules were subjected to in silico protein–ligand docking study against common drug target proteins of SA and MRSA. Among the studied ligands, granatin A demonstrated the highest significance to inhibit topoisomerase IV with a binding energy of −11.3 kcal/mol and produced 7 hydrogen bonds, followed by punicalin with −10.7 kcal/mol binding energy toward penicillin-binding protein 2a with 6 hydrogen bonds. Conclusion: Phytochemicals of T. catappa demonstrates significant drug ability potential against drug-resistant MRSA pathogen and demands further investigation on their individual activity and mechanism.

EVALUATION OF IN-SILICO ANTICANCER POTENTIAL OF PYRETHROIDS: A COMPARATIVE MOLECULAR DOCKING STUDY

2015 ◽  
Author(s):  
Manik Ghosh ◽  
Kamal Kant ◽  
Anoop Kumar ◽  
Padma Behera ◽  
Naresh Rangra ◽  
...  
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Docking Study ◽  
Molecular Docking Study

Development of Xanthine Based Inhibitors Targeting Phosphodiesterase 9A

2017 ◽  
Vol 14 (10) ◽  
pp. 1122-1137 ◽  
Author(s):  
Nivedita Singh ◽  
Parameswaran Saravanan ◽  
M.S. Thakur ◽  
Sanjukta Patra
Keyword(s):  
Free Energy ◽  
Active Site ◽  
Signal Transduction Pathway ◽  
Docking Study ◽  
Primary Objective ◽  
Cgmp Level ◽  
Active Site Residues ◽  
Aromatic Fragment ◽  
Docking Approach ◽  
Free Energy Of Binding

Background: Phosphodiesterases 9A (PDE9A) is one of the prominent regulating enzymes of the signal transduction pathway having highest catalytic affinity for second messenger, cGMP. When the cGMP level is lowered, an uncontrolled expression of PDE9A may lead to various neurodegenerative diseases. To regulate the catalytic activity of PDE9A, potent inhibitors are needed. Objective: The primary objective of the present study was to develop new xanthine based inhibitors targeting PDE9A. This study was an attempt to bring structural diversification in PDE9A inhibitor development because most of the existing inhibitors are constructed over pyrazolopyrimidinone scaffold. Methods: Manual designing and parallel molecular docking approach were used for the development of xanthine derivatives. In this study, N1, N3, N9 and C8 positions of xanthine scaffold were selected as substitution sites to design 200 new compounds. Reverse docking and pharmaceutical analyses were used for final validation of most promising compounds. Results: By keeping free energy of binding cut-off of -6.0 kcal/mol, 52 compounds were screened. The compounds with substitution at N1, N3 and C8 positions of xanthine showed good occupancy in PDE9A active site pocket with a significant interaction pattern. This was further validated by screening different factors such as free energy of binding, inhibition constant and interacting active site residues in the 5Å region. Substitution at C8 position with phenyl substituent determined the inhibition affinity of compounds towards PDE9A by establishing a strong hydrophobic - hydrophobic interaction. The alkyl chain at N1 position generated selectivity of compounds towards PDE9A. The aromatic fragment at N3 position increased the binding affinity of compounds. Thus, by comparative docking study, it was found that compound 39-42 formed selective interaction towards PDE9A over other members of the PDE superfamily. Conclusion: From the present study, N1, N3 and C8 positions of xanthine were concluded as the best sites for substitution for the generation of potent PDE9A inhibitors.

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