Abstract:
:Microtubule affinity regulating kinase 4 (MARK4) plays essential role in the tau-assisted regulation of microtubule dynamics. Over expression of MARK4 causes early phosphorylation of Ser262 of tau protein which is essential for microtubule binding. Hyperphosphorylation of tau protein causes the formation of paired helical fragments and neurofibrillary tangles, the hallmarks of Alzheimer's disease. Targeting the modulation of MARK4 activity is an effective strategy for therapeutic intervention of Alzheimer's and other MARK4 associated neurodegenerative diseases. Having role of pyrazolopyrimidine derivatives in the therapeutic management of neurodegenerative diseases, we have tried to estimate their binding affinity with the MARK4. We performed in silico screening of 59 pyrazolopyrimidine derivatives against MARK4 and obtained a few best possible inhibitors. Molecular docking-based interaction analysis suggested five potential leads that were further analyzed using molecular dynamics simulations, MM/PBSA, principal component analysis and graph theory based dynamic network analysis to observe structural changes caused due to ligand binding. All these computational analyses suggested that compounds with PubChem IDs: 91895678, 91895679, 91895692, 91145515 and 90794095 may be further exploited to address Alzheimer's and other neurodegenerative diseases.Communicated by Ramaswamy H. Sarma.
journal_name
J Biomol Struct Dynjournal_title
Journal of biomolecular structure & dynamicsauthors
Naqvi AAT,Jairajpuri DS,Noman OMA,Hussain A,Islam A,Ahmad F,Alajmi MF,Hassan MIdoi
10.1080/07391102.2019.1666745subject
Has Abstractpub_date
2020-08-01 00:00:00pages
3892-3907issue
13eissn
0739-1102issn
1538-0254journal_volume
38pub_type
杂志文章abstract::Phospholipases A(2) (PLA(2)) are enzymes commonly found in snake venoms from Viperidae and Elaphidae families, which are major components thereof. Many plants are used in traditional medicine as active agents against various effects induced by snakebite. This article presents the PLA(2) BthTX-I structure prediction ba...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2009.10507293
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abstract::The specific interaction between lambda phage Cro repressor and the DNA fragment bearing the consensus sequence of operators has been studied using nuclear magnetic resonance (NMR). Using both 15N- and 13C/15N- labeled lambda-Cro in complex with unlabeled DNA, chemical shift assignments of the lambda-Cro-DNA complex w...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.1999.10508309
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abstract::Within the five classes (α, β, γ, δ, and ζ) of carbonic anhydrases (CAs) the first two, containing mammal and plant representatives, are the most studied among all CAs. In this study, we have focused our investigation on the beta-class carbonic anhydrase of Methanobacterium thermoautotrophicum. We investigated both th...
journal_title:Journal of biomolecular structure & dynamics
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doi:10.1080/07391102.2015.1025100
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journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.1996.10508898
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journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2013.855144
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journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2016.1268977
更新日期:2018-01-01 00:00:00
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journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2012.745821
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journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.1985.10506322
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abstract::Our earlier study on the nucleosomes containing TBP binding sites (TATA boxes) indicated that generally the same sequence, which harbors the TATA box, encodes simultaneously an alternative rotational setting of the box, so that the TATA element is either exposed (position "minor groove out") or hidden in position "min...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2015.1134348
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journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2009.10507324
更新日期:2009-12-01 00:00:00
abstract::Thermodynamic parameters of coaxial stacking at complementary helix-helix interfaces GX*pYG/CZVC (X,Y=A,C,T,G;*-nick) created by contiguous oligonucleotide hybridization were determined. The data obtained were compared to the thermodynamic parameters of coaxial stacking at the interfaces CX*pYC/GZVG. Multiple linear r...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2003.10506940
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abstract::Pebrine is a microsporidian disease caused by Nosema bombycis in Bombyx mori (silk worm) which results in brown/black spots. The affected larvae either spin cocoons which are flimsy with low silk content or not spin a cocoon. It has been hypothesised that Serine Protease Inhibitor 106 (SPN106) is responsible for evasi...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2019.1696704
更新日期:2020-10-01 00:00:00
abstract::An investigation of the self-association behavior of 2'-deoxy[5'-phosphate-guanylyl-(3'-5')-guanosine] (d(pGpG)) in the presence of Na+ and K+ ions has been carried out by 1H and 31P NMR and FTIR spectroscopy. A comparison has been made of the self- association behavior of d(pGpG) with that of the related dinucleotide...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.1999.10508386
更新日期:1999-12-01 00:00:00
abstract::In this study, conformational behavior, structural, and vibrational characterization of the carboxy terminal dipeptide of β-endorphin (glycy-l-glutamine, glycyl-glutamine, beta-endorphin30-31), which is an inhibitory neuropeptide synthesized from beta-endorphin1-31 in brain stem regions, has been investigated. The the...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2016.1154893
更新日期:2017-02-01 00:00:00
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journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.1986.10506341
更新日期:1986-10-01 00:00:00
abstract::At high binding densities acridine orange (AO) forms complexes with ds DNA which are insoluble in aqueous media. These complexes are characterized by high red- and minimal green-luminescence, 1:1 (dye/P) stoichiometry and resemble complexes of AO with ss nucleic acids. Formation of these complexes can be conveniently ...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.1984.10507532
更新日期:1984-06-01 00:00:00
abstract::Multidrug efflux mechanism is the main cause of intrinsic drug resistance in bacteria. Mycobacterium multidrug resistant (MMR) protein belongs to small multidrug resistant family proteins (SMR), causing multidrug resistance to proton (H(+))-linked lipophilic cationic drug efflux across the cell membrane. In the presen...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2013.842185
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journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2018.1439772
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journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2019.1664326
更新日期:2020-08-01 00:00:00
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journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.1994.10508052
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abstract::We study the CaM-peptide interactions for four CaM-related peptides with different calcium equivalents, using the hCaM-M124C-mBBr biosensor and Molecular Dynamics (MD). Due to the high sensitivity of the biosensor, we were able to calculate five Kds based on the number of calcium equivalents for each peptide, showing ...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
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abstract::Culex quinquefasciatus Cqm1 protein acts as the receptor for Lysinibacillus sphaericus mosquito-larvicidal binary (BinAB) toxin that is used worldwide for mosquito control. We found amino acid transporter protein, rBAT, as phylogenetically closest Cqm1 homolog in humans. The present study reveals large evolutionary di...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2020.1784792
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journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2018.1491424
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abstract::New tailored Cu(II) & Zn(II) metal-based antitumor drug entities were synthesized from substituted benzothiazole o‒vanillin Schiff base ligands. The complexes were thoroughly characterized by elemental analysis, spectroscopic studies {IR, 1H & 13C NMR, ESI-MS, EPR} and magnetic susceptibility measurements. The structu...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2018.1467794
更新日期:2019-04-01 00:00:00
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journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2018.1456362
更新日期:2019-03-01 00:00:00
abstract::Most β-Glucosidase (B8CYA8) are prone to inhibition by glucose. Experimentally observed specific activity of B8CYA8 on 20 mM, 50 mM, and 100 mM p-nitrophenyl-β-D-glucopyranoside (pNPGlc) substrate concentrations show surprise dependence on the presence of 0-3 M glucose at 335 K. We found that at high substrate concent...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2020.1796789
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abstract::CLTOAB is an ammonium-based ionic liquid composed of ε-Caprolactam (CL) C6H11NO and tetraoctylammonium bromide (TOAB) (C32H68BrN). In this study, experimental IR and Raman spectra of CLTOAB ionic liquid together with the computational results of the compound have been reported. The optimized geometry, vibrational freq...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2018.1495578
更新日期:2019-07-01 00:00:00
abstract::Monte-Carlo simulation of poly(dA).poly(dT) hydration by 30 water molecules per nucleotide pair has been performed. Two B-family conformations, both with a 36 degrees helical twist but with different minor groove widths, were considered. One conformation is Arnott's standard B form, the other one is specific for poly(...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.1988.10506508
更新日期:1988-12-01 00:00:00
abstract::We would be tempted to state that there has never been a Levinthal paradox. Indeed, Levinthal raised an interesting problem about protein folding, as he realized that proteins have no time to explore exhaustively their conformational space on the way to their native structure. He did not seem to find this paradoxical ...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2002.10506850
更新日期:2002-12-01 00:00:00
abstract::The solution structure of two double helical nucleic acid fragments, viz, r(CGCGCG) and d(CGCGCG), was probed by means of two-dimensional nuclear Overhauser effect spectroscopy. The two compounds were selected as models for the A-type and B-type double helical conformations, respectively, and it is shown that for each...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.1984.10507572
更新日期:1984-10-01 00:00:00