Molecular Docking and Interaction Studies of Identified Abscisic Acid Receptors in Oryza sativa: An In-Silico Perspective on Comprehending Stress Tolerance Mechanisms

2021 ◽  
Vol 23 ◽  
Author(s):  
Vidya Niranjan ◽  
Amulya Rao ◽  
B Janaki ◽  
Akshay Uttarkar ◽  
Anagha S Setlur ◽  
...  
Keyword(s):  
Oryza Sativa ◽  
Abscisic Acid ◽  
Molecular Docking ◽  
Conformational Changes ◽  
Docking Studies ◽  
Protein Docking ◽  
Ligand Docking ◽  
Simulation Studies ◽  
Naturally Occurring ◽  
Aba Receptors

Background: Abiotic stresses affect plants in several ways and as such, phytohormones such as abscisic acid (ABA) play an important role in conferring tolerance towards these stresses. Hence, to comprehend the role of ABA and its interaction with receptors of the plants, a thorough investigation is essential. Aim: The current study aimed to identify the ABA receptors in Oryza sativa, to find the receptor that binds best with ABA and to examine the mutations present to help predict better binding of the receptors with ABA Methods: Protein sequences of twelve PYL (Pyrabactin resistance 1) and seven PP2C (type 2C protein phosphatase) receptors were retrieved from Rice Annotation Project database and their 3D structures were predicted using RaptorX. Protein-ligand molecular docking studies between PYL and ABA was performed using AutoDock 1.5.6, followed by 100ns molecular dynamic simulation studies using Desmond to determine the acceptable conformational changes after docking via root mean square deviation RMSD plot analysis. Protein-protein docking was then carried out in three sets: PYL-PP2Cs, PYL-ABA-PP2C and PYL(mut)-ABA-PP2C to scrutinize changes in structural conformations and binding energies between complexes. The amino acids of interest were mapped at its respective genomic coordinates using SNP-seek database to ascertain if there were any naturally occurring single nucleotide polymorphisms (SNPs) responsible for triggering rice PYLs mutations Results: Initial protein-ligand docking studies revealed good binding between the complexes, wherein PYL6-ABA complex showed the best energy of -8.15 kcal/mol. The 100ns simulation studies revealed changes in the RMSD values after docking, indicating acceptable conformational changes. Furthermore, mutagenesis study performed at specific PYL-ABA interacting residues followed by downstream PYL(mut)-ABA-PP2C protein-protein docking results after induction of mutations demonstrated a binding energy of -8.17 kcal/mol for PP2C79-PYL11-ABA complex. No naturally occurring SNPs that were responsible for triggering rice PYL mutations were identified when specific amino acid coordinates were mapped at respective genomic coordinates. Conclusion: Thus, the present study provides valuable insights on the interactions of ABA receptors in rice and induced mutations in PYL11 that can enhance the downstream interaction with PP2C

scholarly journals Molecular Docking and Molecular Dynamics Simulation Studies of Triterpenes from Vernonia patula with the Cannabinoid Type 1 Receptor

2021 ◽  
Vol 22 (7) ◽  
pp. 3595
Author(s):  
Md Afjalus Afjalus Siraj ◽  
Md. Sajjadur Rahman ◽  
Ghee T. Tan ◽  
Veronique Seidel
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Molecular Dynamics Simulation ◽  
Binding Affinity ◽  
Docking Studies ◽  
Dynamics Simulation ◽  
Simulation Studies ◽  
Cannabinoid Type 1 Receptor ◽  
Docking Approach

A molecular docking approach was employed to evaluate the binding affinity of six triterpenes, namely epifriedelanol, friedelin, α-amyrin, α-amyrin acetate, β-amyrin acetate, and bauerenyl acetate, towards the cannabinoid type 1 receptor (CB1). Molecular docking studies showed that friedelin, α-amyrin, and epifriedelanol had the strongest binding affinity towards CB1. Molecular dynamics simulation studies revealed that friedelin and α-amyrin engaged in stable non-bonding interactions by binding to a pocket close to the active site on the surface of the CB1 target protein. The studied triterpenes showed a good capacity to penetrate the blood–brain barrier. These results help to provide some evidence to justify, at least in part, the previously reported antinociceptive and sedative properties of Vernonia patula.

scholarly journals Novel inhibitors designing against the potential drug target of Plasmodium falciparum M17 Leucyl Aminopeptidase - PfM17LAP

2021 ◽  
Author(s):  
Govinda Rao Dabburu ◽  
Manish Kumar ◽  
Naidu Subbarao
Keyword(s):  
Plasmodium Falciparum ◽  
Molecular Docking ◽  
Drug Target ◽  
Docking Studies ◽  
Simulation Studies ◽  
Docking Analysis ◽  
Discovery Studio ◽  
Potential Inhibitors ◽  
Key Words Malaria ◽  
Leucyl Aminopeptidase

Abstract: Malaria is one of the major disease of concern worldwide especially in the African regions. According to the recent WHO reports, African regions share 95% of the total deaths worldwide that occurs due to malaria. Plasmodium falciparum M17 Leucyl Aminopeptidase (PfM17LAP) plays an important role in the regulation of amino acids release and for the survival of the parasite. We performed molecular docking and simulation studies to find the potential inhibitors against PfM17LAP using ChEMBL antimalarial library. Molecular docking studies and post-docking analysis revealed that molecules CHEMBL369831 and CHEMBL176888 showed better binding than the reference molecule BESTATIN. LibDock and X-SCORES of molecules BES, CHEMBL369831 and CHEMBL176888 are 130.071, 230.38, 223.56 and -8.75 Kcal/mol, -10.90 Kcal/mol, -11.05 Kcal/mol respectively. ADMET profiling of the top ten ranked molecules was done by using the Discovery Studio. Molecular dynamic studies revealed that the complex PfM17LAP-CHEMBL369831 is stable throughout the simulation. Finally, we have reported novel inhibitors which possess more binding affinity towards PfM17LAP. Key words: Malaria, M17 Leucyl Aminopeptidase, ADMET, X-SCORE

Recent Advancements in Docking Methodologies

Oncology ◽  
2017 ◽  
pp. 848-875
Author(s):  
Vijay Kumar Srivastav ◽  
Vineet Singh ◽  
Meena Tiwari
Keyword(s):  
Molecular Docking ◽  
Binding Free Energy ◽  
Binding Mode ◽  
Docking Studies ◽  
Protein Docking ◽  
Scoring Functions ◽  
Discovery Process ◽  
Ligand Complex ◽  
Small Molecule Databases ◽  
Homology Models

Nowadays molecular docking has become an important methodology in CADD (Computer-Aided Drug Design)-assisted drug discovery process. It is an important computational tool widely used to predict binding mode, binding affinity and binding free energy of a protein-ligand complex. The important factors responsible for accurate results in docking studies are correct binding site prediction, use of suitable small-molecule databases, consistent docking pose, high dock score with good MD (Molecular Dynamics), clarity whether the compound is an inhibitor or agonist, etc. However, still there are several limitations which make it difficult to obtain accurate results from docking studies. In this chapter, the main focus is on recent advancements in various aspects of molecular docking such as ligand sampling, protein flexibility, scoring functions, fragment docking, post-processing, docking into homology models and protein-protein docking.

scholarly journals Ligand docking and binding site analysis with pymol and autodock/vina

2015 ◽  
Vol 4 (2) ◽  
pp. 168 ◽  
Author(s):  
Mohd. Ahmar Rauf ◽  
Swaleha Zubair ◽  
Asim Azhar
Keyword(s):  
Molecular Docking ◽  
Drug Design ◽  
Three Dimensional ◽  
Structural Features ◽  
Docking Studies ◽  
Ligand Docking ◽  
Structure Based Drug Design ◽  
Site Analysis ◽  
User Friendly ◽  
Autodock 4.2

<p>Docking of various therapeutically important chemical entities to the specific target sites offers a meaningful strategy that may have tremendous scope in a drug design process. For a thorough understanding of the structural features that determine the strength of bonding between a ligand with its receptor, an insight to visualize binding geometries and interaction is mandatory. Bioinformatical as well as graphical software ‘PyMOL’ in combination with the molecular docking suites Autodock and Vina allows the study of molecular combination to visualize and understand the structure-based drug design efforts. In the present study, we outlined a user friendly method to perform molecular docking using vina and finally the results were analyzed in pymol in both two as well as three-dimensional orientation. The operation bypasses the steps that are involved in docking using cygwin terminal like formation of gpf and dpf files. The simple and straight-forward operation method does not require formal bioinformatics training to apprehend molecular docking studies using AutoDock 4.2 program.</p>

scholarly journals SEARCHING ANTIVIRAL DRUGS FOR EBOLA VIRUS FROM PHYTO-CONSTITUENTS OF AZADIRACHTA INDICA: APPLICATION OF MOLECULAR MODELING STUDIES

2017 ◽  
Vol 10 (7) ◽  
pp. 254
Author(s):  
P Parasuraman ◽  
Suresh R ◽  
Perumal P
Keyword(s):  
Azadirachta Indica ◽  
In Silico ◽  
Ebola Virus ◽  
Docking Studies ◽  
Binding Activity ◽  
Ligand Docking ◽  
In Silico Docking ◽  
Naturally Occurring ◽  
Molecular Modeling Studies ◽  
Further Development

 ABSTRACTThe current objective of the study is to identify some naturally occurring product from Azadirachta indica and evaluate its binding activity against VP24 protein as Ebola virus target through in silico docking studies. Reported phytoconstituents of Azadirachta indica were prepared for docking evaluation using Brincidofovir as the standard. In silico docking studies were carried out using GLIDE (Grid-based Ligand Docking with Energetics) is a ligand binding program provided by Schrödinger. These results showed that all the selected phytoconstituents showed binding energy ranging between -7.95 kcal/mol to -1.54 kcal/mol when compared with that of the standard (-6.06 kcal/mol). Naturally occurring products Catechin, Epicatechin, Gallic acid and Nimbolide are potential than the standard brincidofovir but Azadirachtin, Margolonone, Mahmoodin, Isomargolonone, Gedunin, Margolone, Nimbidin and Nimbin have low binding affinity towards target when compared with the standard. These molecular docking analyses of phytoconstituents of Azadirachta indica could lead to the further development to identify the potent drugs for the treatment of Ebola virus. KEYWORDS: Azadirachta indica, VP42 protein, Ebola virus, in silico docking.   

scholarly journals Molecular Docking Studies of Coronavirus Proteins with Medicinal Plant Based Phytochemicals

2021 ◽  
Vol 6 (1) ◽  
pp. 57-63
Author(s):  
Avinash Marwal ◽  
Mukesh Meena ◽  
RK Gaur
Keyword(s):  
Molecular Docking ◽  
Medicinal Plant ◽  
Rna Binding ◽  
Data Bank ◽  
Black Pepper ◽  
Docking Studies ◽  
Ligand Docking ◽  
Main Protease ◽  
Pubchem Database ◽  
In Silico Molecular Docking

In this study, we presented an in silico molecular docking between the SARS-CoV-2 four proteins [(a) SARS-CoV-2 nucleocapsid protein N-terminal RNA binding domain (6M3M), (b) Nsp9 RNA binding protein of SARS CoV-2 (6W4B), (c) The crystal structure of COVID-19 main protease in apo form (6M03), and (d) Structure of the 2019-nCoV HR2 Domain (6LVN)] available in the PDB (Protein Data Bank), and the medicinal plant-based phytochemicals (retrieved from PubChem database) as ligand molecules i.e. Piperine (Black Pepper), Eugenol (Clove), Alliin (Garlic), Gingerol (Ginger) and Curcumin (Turmeric). All these ligand molecules showed good docking with their respective receptor molecules and their scores range from -8.195 to -5.263. DockThor Portal (a receptor ligand-docking server) which was recently developed and published this year were used in the current study. The obtained results might help in the wet lab conditions to develop better antiviral compounds against SARS-CoV-2.

scholarly journals Immune escape facilitation by mutations of epitope residues in RdRp of SARS-CoV-2

2021 ◽  
Author(s):  
Aayatti Mallick Gupta ◽  
Sasthi Charan Mandal ◽  
Jaydeb Chakrabarti ◽  
Sukhendu Mandal
Keyword(s):  
Conformational Changes ◽  
Md Simulation ◽  
Immune Escape ◽  
Dihedral Angles ◽  
Radius Of Gyration ◽  
Simulation Studies ◽  
Epitope Region ◽  
Naturally Occurring ◽  
Intramolecular Hydrogen ◽  
Opening Up

SARS-CoV-2 has considerably higher mutation rate. SARS-CoV-2 possesses a RNA dependent RNA polymerase (RdRp) which helps to replicate its genome. The mutation P323L in RdRp is associated with the loss of a particular epitope (321-327) from this protein which may influence the pathogenesis of the concern SARS-CoV-2 through the development of antibody escape variants. We consider the effect of mutations in some of the epitope regions including the naturally occurring mutation P323L on the structure of the epitope and their interface with paratope using all-atom molecular dynamics (MD) simulation studies. P323L mutations cause conformational changes in the epitope region by opening up the region associated with increase in the radius of gyration and intramolecular hydrogen bonds, making the region less accessible. Moreover, the fluctuations in the dihedral angles in the epitope:paratope (IgG) interface increase which destabilize the interface. Such mutations may help in escaping antibody mediated immunity of the host.

scholarly journals Modeling and Molecular Docking Studies on Alangium salvifolium (Alanginaceae) as a Target for Anti-oxidant Enzyme

2019 ◽  
pp. 1-11
Author(s):  
Mohammad Nadeem Khan
Keyword(s):  
Molecular Docking ◽  
Antioxidant Activities ◽  
Docking Studies ◽  
Energy Simulation ◽  
Scavenging Activity ◽  
Simulation Studies ◽  
Ros Scavenging ◽  
Anti Oxidant ◽  
First Time ◽  
Antioxidant Effects

Objectives: The present studies pursue at retrieve and draws the active phytocompounds structure of Alangium salvifolium and assessing its simulation anti-oxidant enzyme activities. Methods: Retrieve/draws of the compounds were carried out using chem.-sketch software. The 3-D structures of the Phytocompounds were visualized based upon the UV, NMR spectral data along with their energy simulation studies. The antioxidant and enzyme simulation activity were evaluated in-silico using the ACD labs,PyRx, RASMOL,PYMOL,Aragslab and Discovery 3.1 studio. Key Findings: Phytochemicals structure drawing of A. salvifolium resulted in the structured and recognition of four phytochemicals. The plant phytochemicals showed significant anti-oxidant enzymes activity enhancer and ROS eliminator through binding to its metal domain receptor. Conclusion: Phytochemicals were drawing from A. salvifolium. To the best of our knowledge, among these phytochemicals, were studied anti-oxidant enzymes metals binding domain to increase the ROS scavenging activity for the foremost time from mimic with molecular docking. Moreover, study of phytochemicals simulation was for the first time from this plant. The plant revealed auspicious increase the antioxidant activities virtual screening. This gives thinking to some of its pharmacological properties and suggests additional antioxidant effects, for as a scavenger as well as anti-oxidant enzyme stimulator, which have not been reported yet.

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