Homology modeling, molecular docking and MD simulation studies to investigate role of cysteine protease from Xanthomonas campestris in degradation of Aβ peptide

Dhanavade, Maruti J.; Jalkute, Chidambar B.; Barage, Sagar H.; Sonawane, Kailas D.

doi:10.1016/j.compbiomed.2013.09.021

Cited by 52 publications

(33 citation statements)

References 50 publications

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“…The kollman united atom charges were assigned to receptor atom and charges of zinc interacting residues were manually checked. The zinc parameters like zinc radius, well depth and charges were assigned as per the earlier literature Xin and William 2003) similarly as used in our previous studies (Barage and Sonawane 2014;Dhanavade et al 2013;Dhanavade and Sonawane 2014). The active site was defined using AutoGrid (Morris et al 2009).…”

Section: Molecular Dockingmentioning

confidence: 99%

Identification of Angiotensin Converting Enzyme Inhibitor: An In Silico Perspective

Jalkute

Barage

Dhanavade

et al. 2014

Int J Pept Res Ther

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Angiotensin Converting Enzyme (ACE) regulates blood pressure and electrolyte balance by converting angiotensin I into angiotensin II, which acts as vasoconstrictor and aldosterone-stimulating peptide. ACE is also known to inactivate vasodilators, bradykinin and angiotensin 1-7 peptide. Thus, the down-regulation of ACE activity would be very beneficial in various cardiovascular diseases. In present in silico approach, virtual screening was performed to identify possible novel inhibitors of testis ACE (tACE) from ZINC database using Dockblaster. All screened compounds were filtered through Lipinski's rules and other properties. PyRx tool was then implemented to dock selected compounds. Finally, ligand ZINC48251687 re-docked using Autodock 4.2 with His 383, His 387 and Glu 411 as flexible residues of tACE. Molecular Dynamics simulation was then carried out to investigate the binding stability of the screened ligand in a dynamic environment. It has been observed that tACE-ligand complex was quite stable over the entire simulation run. We found that ligand was stabilized by strong hydrogen bonding interactions with Ala 354, Ala 356, Tyr 523 and Zn 2? of tACE. Thus, ZINC48251687 could be used as starting point for the development of new non-peptidic inhibitor of tACE and for designing drug against cardiovascular and related renal diseases.

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Section: Molecular Dockingmentioning

confidence: 99%

Identification of Angiotensin Converting Enzyme Inhibitor: An In Silico Perspective

Jalkute

Barage

Dhanavade

et al. 2014

Int J Pept Res Ther

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“…The docking study of ArnA protein with its substrate UDP-GlcA was carried out using PATCHDOCK online program (Duhovny et al 2002) similar to earlier studies (Barage and Sonawane 2013; Dhanavade et al 2013;Dhanavade and Sonawane 2014;Jalkute et al 2013;Parulekar et al 2013;Tseng et al 2007). PATCHDOCK is geometry based molecular docking algorithm which aims in finding docking transformations that yield good molecular shape complementarity based on its default constraints assigned for docking such as clustering RMSD, complex type, potential binding sites of receptor and distance constraints.…”

Section: Substrate and Inhibitor Docking Studiesmentioning

confidence: 99%

Homology modeling and molecular docking studies of ArnA protein from Erwinia amylovora: role in polymyxin antibiotic resistance

Sonawane

Parulekar

Malkar

et al. 2014

J. Plant Biochem. Biotechnol.

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The resistivity of plant pathogen Erwinia amylovora against the polymyxin group of antibiotics is enhanced by modification of lipid A from lipopolysaccharide with 4-amino-4-deoxy L-arabinose (Ara4N) catalyzed by a bifunctional protein ArnA. ArnA is the first enzyme in the lipid A modification pathway with distinct dehydrogenase and transformylase domains which has been known in development of resistivity to polymyxin group of antibiotics. Thus, three dimensional structure of ArnA protein from Erwinia amylovora was constructed using homology modeling technique. The quality and reliability of the generated 3-D model was then assessed by different online available programs such as What if, PROCHECK, QMEAN, ProSA along with superimposition by UCSF Chimera. Sequence analysis study of ArnA protein from E. coli, Erwinia amylovora, Yersinia pestis, Ps. aeruginosa and Salmonella showed conserved domains with exact active site residues. Molecular docking study of ArnA protein with substrate UDP-GlcA and different inhibitors such as 5-formyl-5,6,7,8 tetrahydrofolate, leucovorin and 5-methyl tetrahydrofolate revealed similar binding pocket. The residues ASN492, ARG510, SER433 and ARG619 of ArnA protein are involved in interactions with inhibitors. Thus, this study could be useful to understand the proper binding mode of inhibitors to inhibit the lipid A modification pathway of ArnA protein from plant pathogen Erwinia amylovora.

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“…Dhanavade et al [108] studied through comparative modeling a cysteine protease present in Xhantomonas campestris the active site of which contains a set of residues practically identical to human cathepsin B enzyme (hCB), the activity of which contributes to the reduction of the β-amyloid peptide by proteolytic cleavage of Aβ1-42, offering a protective role against AD [109]. The homology model was used in docking analysis with the β-amyloid peptide, demonstrating a favorable interaction between the Cys17 of the protease with the Lys16 of the peptide, evidencing a putative β-amyloid cleavage-site.…”

Section: Drug Design and Discovery Targeting Nddmentioning

confidence: 99%

Theoretical and Experimental Approaches Aimed at Drug Design Targeting Neurodegenerative Diseases

et al. 2019

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In recent years, green chemistry has been strengthening, showing how basic and applied sciences advance globally, protecting the environment and human health. A clear example of this evolution is the synergy that now exists between theoretical and computational methods to design new drugs in the most efficient possible way, using the minimum of reagents and obtaining the maximum yield. The development of compounds with potential therapeutic activity against multiple targets associated with neurodegenerative diseases/disorders (NDD) such as Alzheimer’s disease is a hot topic in medical chemistry, where different scientists from various disciplines collaborate to find safe, active, and effective drugs. NDD are a public health problem, affecting mainly the population over 60 years old. To generate significant progress in the pharmacological treatment of NDD, it is necessary to employ different experimental strategies of green chemistry, medical chemistry, and molecular biology, coupled with computational and theoretical approaches such as molecular simulations and chemoinformatics, all framed in the rational drug design targeting NDD. Here, we review how green chemistry and computational approaches have been used to develop new compounds with the potential application against NDD, as well as the challenges and new directions of the drug development multidisciplinary process.

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Homology modeling, molecular docking and MD simulation studies to investigate role of cysteine protease from Xanthomonas campestris in degradation of Aβ peptide

Cited by 52 publications

References 50 publications

Identification of Angiotensin Converting Enzyme Inhibitor: An In Silico Perspective

Identification of Angiotensin Converting Enzyme Inhibitor: An In Silico Perspective

Homology modeling and molecular docking studies of ArnA protein from Erwinia amylovora: role in polymyxin antibiotic resistance

Theoretical and Experimental Approaches Aimed at Drug Design Targeting Neurodegenerative Diseases

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