Molecular docking and molecular dynamics simulation approach to screen natural compounds for inhibition of <i>Xanthomonas oryzae pv. Oryzae</i> by targeting peptide deformylase

Joshi, Tushar; Joshi, Tanuja; Sharma, Priyanka; Chandra, Subhash; Pande, Veena

doi:10.1080/07391102.2020.1719200

Cited by 75 publications

(35 citation statements)

References 39 publications

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“…Therefore, the only protein, as well as the protein-ligand complexes, showed a relatively consistent and similar value of R g confirming that all the three systems have stable conformation. Similarly, in an earlier study, the stability and compactness were observed for both native protein as well as protein-ligand complexes of peptide deformylase from Xanthomonas oryzae upon MD simulation [58]. The RMSF plot indicated that most of the residues in the only PsGH3 and protein-ligand complexes showed a similar pattern of fluctuations throughout the simulation (Fig.…”

Section: Molecular Dynamics Of Protein-ligand Complexessupporting

confidence: 79%

“…8a). A similar pattern of RMSD was obtained for native as well as the protein-ligand complexes of peptide deformylase from Xanthomonas oryzae upon MD simulation [58]. Therefore, from the RMSD plot, it was evident that the protein as well as the protein-ligand complexes reached equilibrium at 80 ns and thus could be considered for further analysis.…”

Section: Molecular Dynamics Of Protein-ligand Complexessupporting

confidence: 70%

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Structure and dynamics analysis of multi-domain putative β-1,4-glucosidase of family 3 glycoside hydrolase (PsGH3) from Pseudopedobacter saltans

Nath

Goyal

2021

J Mol Model

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Structure and conformational behaviour of a putative β-1,4-glucosidase of glycoside hydrolase family 3 ( Ps GH3) from Pseudopedobacter saltans was predicted by using in-silico tools. Ps GH3 modeled structure constructed using Phyre2 displayed multidomain architecture comprising an N-terminal ( β / α ) 8 -fold domain followed by ( α / β ) 6 -sandwich domain, PA14 domain, and a C-terminal domain resembling an immunoglobulin fold. Ramachandran plot displayed 99.3% of amino acids in the allowed region and 0.7% residues in the disallowed region. Multiple sequence alignment (MSA) and structure superposition of Ps GH3 with other homologues from GH3 family revealed the conserved residues, Asp274 and Glu624 present in loops LA and LB, respectively originating from N-terminal domain act as catalytic residues. The volume and area calculated for Ps GH3 displayed a deep active-site conformation comparable with its homologues, β-1,4-glucosidases (GH3) of Kluyveromyces marxianus and Streptomyces venezuelae. Molecular dynamic (MD) simulation of Ps GH3 structure for 80 ns suggested stable and compact structure. Molecular docking studies revealed deeper active site conformation of Ps GH3 that could house larger cellooligosaccharides up to 7° of polymerization (DP7). The amino acid residues, Ala86, Leu88, Cys275, Pro483, Phe493, Asn417, Asn491, Pro492, and Leu495 created a binding pocket near the catalytic cleft, crucial for ligand binding. MD simulation of Ps GH3 in the presence of cellooligosaccharides, viz., cellobiose and celloheptaose showed stability in terms of RMSD, R g , and SASA values till 80 ns. The calculation of average number of hydrogen bond (H-bond), interaction energy, and binding free energy confirmed the stronger binding affinity of the larger cellooligosaccharides such as celloheptaose in the binding cavity of Ps GH3.

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Section: Molecular Dynamics Of Protein-ligand Complexessupporting

confidence: 79%

Section: Molecular Dynamics Of Protein-ligand Complexessupporting

confidence: 70%

Structure and dynamics analysis of multi-domain putative β-1,4-glucosidase of family 3 glycoside hydrolase (PsGH3) from Pseudopedobacter saltans

Nath

Goyal

2021

J Mol Model

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“…The superimposed 2-dimensional structure is shown in Figure 14 , the superimposed amino acids of the complexes are encircled in red. This partially proved the efficiency and validity of the docking protocol (Joshi et al., 2020 ).…”

Section: Resultsmentioning

confidence: 65%

Molecular docking, validation, dynamics simulations, and pharmacokinetic prediction of natural compounds against the SARS-CoV-2 main-protease

Shivanika

Kumar²,

Ragunathan

et al. 2020

Journal of Biomolecular Structure and Dynamics

172

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The study aims to evaluate the potency of two hundred natural antiviral phytocompounds against the active site of the Severe Acquired Respiratory Syndrome-Coronavirus À 2 (SARS-CoV-2) Main-Protease (M pro) using AutoDock 4.2.6. The three-dimensional crystal structure of the M pro (PDB Id: 6LU7) was retrieved from the Protein Data Bank (PDB), the active site was predicted using MetaPocket 2.0. Food and Drug Administration (FDA) approved viral protease inhibitors were used as standards for comparison of results. The compounds theaflavin-3-3'-digallate, rutin, hypericin, robustaflavone, and (-)-solenolide A with respective binding energy of À12.41 (Ki ¼ 794.96 pM); À11.33 (Ki ¼ 4.98 nM); À11.17 (Ki ¼ 6.54 nM); À10.92 (Ki ¼ 9.85 nM); and À10.82 kcal/mol (Ki ¼ 11.88 nM) were ranked top as Coronavirus Disease À 2019 (COVID-19) M pro inhibitors. The interacting amino acid residues were visualized using Discovery Studio 3.5 to elucidate the 2-dimensional and 3-dimensional interactions. The study was validated by i) re-docking the N3-peptide inhibitor-M pro and superimposing them onto co-crystallized complex and ii) docking decoy ligands to M pro. The ligands that showed low binding energy were further predicted for and pharmacokinetic properties and Lipinski's rule of 5 and the results are tabulated and discussed. Molecular dynamics simulations were performed for 50 ns for those compounds using the Desmond package, Schr€ odinger to assess the conformational stability and fluctuations of protein-ligand complexes during the simulation. Thus, the natural compounds could act as a lead for the COVID-19 regimen after in-vitro and in-vivo clinical trials.

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“…The authors have analyzed the binding of screened noscapines with the protease of SARS-CoV-2 using trajectories to understand the stability and flexibility. The trajectories like root mean square deviation (RMSD), root mean square fluctuation (RMSF), HBs and change in binding free energy calculation will be determined by AMBER18 (Alexandrescu et al, 2001;David et al, 2005;Joshi et al, 2020). RMSD plot is usually used to understand the stability of the complex as in Equation (3) while RMSF is used to understand the structural flexibility.…”

Section: Target and Ligand Preparationsmentioning

confidence: 99%

Understanding the binding affinity of noscapines with protease of SARS-CoV-2 for COVID-19 using MD simulations at different temperatures

Kumar

Kumari

Jayaraj

et al. 2020

Journal of Biomolecular Structure and Dynamics

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The current outbreak of a novel coronavirus, named as SARS-CoV-2 causing COVID-19 occurred in 2019, is in dire need of finding potential therapeutic agents. Recently, ongoing viral epidemic due to coronavirus (SARS-CoV-2) primarily affected mainland China that now threatened to spread to populations in most countries of the world. In spite of this, there is currently no antiviral drug/ vaccine available against coronavirus infection, COVID-19. In the present study, computer-aided drug design-based screening to find out promising inhibitors against the coronavirus (SARS-CoV-2) leads to infection, COVID-19. The lead therapeutic molecule was investigated through docking and molecular dynamics simulations. In this, binding affinity of noscapines(23B)-protease of SARS-CoV-2 complex was evaluated through MD simulations at different temperatures. Our research group has established that noscapine is a chemotherapeutic agent for the treatment of drug resistant cancers; however, noscapine was also being used as anti-malarial, anti-stroke and cough-suppressant. This study suggests for the first time that noscapine exerts its antiviral effects by inhibiting viral protein synthesis. ARTICLE HISTORY

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Molecular docking and molecular dynamics simulation approach to screen natural compounds for inhibition of Xanthomonas oryzae pv. Oryzae by targeting peptide deformylase

Cited by 75 publications

References 39 publications

Structure and dynamics analysis of multi-domain putative β-1,4-glucosidase of family 3 glycoside hydrolase (PsGH3) from Pseudopedobacter saltans

Structure and dynamics analysis of multi-domain putative β-1,4-glucosidase of family 3 glycoside hydrolase (PsGH3) from Pseudopedobacter saltans

Molecular docking, validation, dynamics simulations, and pharmacokinetic prediction of natural compounds against the SARS-CoV-2 main-protease

Understanding the binding affinity of noscapines with protease of SARS-CoV-2 for COVID-19 using MD simulations at different temperatures

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