Wyniki wyszukiwania - BazTech

1

Nitrosubstituted analogs of isoxazolines and isoxazolidines: a surprising estimation of their biological activity via molecular docking

Zawadzińska Karolina, Gostyński Bartłomiej

Scientiae Radices

|

2023

|

Vol. 2, Iss. 1

25--46

EN

The biological activities in the field of antimicrobial application of trihalomethylated isoxazolines and isoxazolidines were investigated by means of molecular docking. In our work, we compared these two groups of heterocyclic compounds due to their strength of non-covalent binding affinity with several exemplary proteins that are known to partake in various biological processes. The obtained results show that the investigated compounds possess higher binding affinities to selected proteins than many hitherto known and applied compounds.

2

Synthesis, molecular modelling and antibacterial activity of 4-aryl-thiosemicarbazides

Bhat Mashooq Ahmad, Naglah Ahmad M., Khan Azmat Ali, Al-Dhfyan Abdullah

Polish Journal of Chemical Technology

|

2022

|

Vol. 24, nr 1

39--46

EN

N-Substituted phenyl/cyclohexyl-2-(pyridine-4-carbonyl) hydrazine-1-carbothioamides (2a–r) were synthesized, characterized by spectral and analytical data. The compounds were evaluated for antibacterial activity by the discdiffusion method. Most of the compounds showed activity against Gram-positive bacteria. Compound 2h with 4-Sulfapyrimidine phenyl substitution was found to be the most promising candidate, active against Gram-positive and methicillin-resistant Staphylococcus aureus (MRSA) strains with minimum inhibitory concentration (MIC) of (2–7 μg/mL). From the docking study, we predicted that compounds (2r, 2g, 2h, 2o, 2p and 2e) possess better antibacterial activity by having a good binding affinity with target protein and they could be used as potential drugs as antimicrobials. Amongst all the docked compounds, the compound 2h presented near binding affinity & interaction docking score with DNA gyrase enzymes with reference to ciprofoxacin.

3

Synthesis and spectroscopic interpretations of Co(II), Ni(II) and Cu(II) decxycholate complexes with molecular docking of COVId-19 protease

Refat Moamen S., Bakare Safyah B., Altalhi Tariq A., Alam Kehkashan, Al-Hazmi Ghaferah H.

Polish Journal of Chemical Technology

|

2021

|

Vol. 23, nr 2

54--59

EN

Co(II), Ni(II) and Cu(II) decxycholate complexes are interesting due to their biologically active and deliberate interest in the research due to their coordination properties. The microanalytical ‘elemental analysis’, molar conductivity, (infrared and Raman) spectroscopy, thermal analyses (TGA/DSC), UV-vis spectra, and ESR for copper(II) decxycholate complex investigations were performed in the structural assignments of Co(II), Ni(II) and Cu(II) decxycholate complexes. Reaction of the sodium deoxycholate ligand (C24H39O4Na) with three transition metal ions form the complexes of formulae, [M(C24H39O4)2(H2O)2] . xH2O where M = Co(II), Ni(II) and Cu(II) where x = 2 for Cu(II) and x = 4 in case of M = Co(II) or Ni(II) metal ions. The FTIR spectra of the complexes show that decxycholate molecule is present as bidentate ligand. Molecular docking utilizing to additionally examine the interaction of COVID-19 (6LU7) with different complexes of deoxycholic acid with Co(II), Ni(II) and Cu(II). Furthermore, in the case of Co(II) deoxycholate complex, the probe is surrounded by amino residues Met235, Pro241, Glu240, Pro108, Gln110, Phe294, and Ile152. The probe molecule of Ni(II) deoxycholate complex is sited close to amino acids Tyr126, Tyr239, Leu287, Leu272, and Lys137. For, Cu(II) deoxycholate complex, the residues of amino acids comprise of Pro132, Pro108, Gln110, Gly109, Ile200, Asn203, Val202, His246, Pro293 and Tyr154. The binding energy was determined from the docking reads for Co(II)–6LU7, Ni(II)–6LU7 and Cu(II)–6LU7 deoxycholate compounds were found to be −446.99, −500.52, −398.13 kcal mol−1 individually.

4

Effects of herbicides and fungicides on the soil chitinolytic activity. A molecular docking approach

Vlădoiu D. L., Nicoleta Filimon M. N., Ostafe V., Isvoran A.

Ecological Chemistry and Engineering. S

|

2015

|

Vol. 22, nr 3

439--450

EN

A molecular docking study was undertaken using the programs SwissDock and PatchDock to assess the interactions of the bacterial chitinases belonging to the GH18 and GH19 families with two herbicides (chlorsulfuron and nicosulfuron) and two fungicides (difenoconazole and drazoxolon). Both molecular docking programs predict that all considered pesticides bind to the active sites of chitinases produced by soil microorganisms. There are correlations for predicted binding energy values for receptor-ligand complexes obtained using the two programs consolidating the prediction of the chitinases-pesticides interactions. The interactions of chitinases with pesticides involve the same residues as their interactions with known inhibitors suggesting the inhibitory potential of pesticides. Pesticides interact stronger with chitinases belonging to the GH18 family, their active sites reflecting higher polarity than those of the GH19 chitinases. Also, herbicides reveal a higher inhibitory potential to bacterial chitinases than fungicides.

PL

W celu oceny oddziaływań chitynaz bakteryjnych należących do rodziny GH18 i GH19 z dwoma herbicydami (chlorosulfuron i nikosulfuron) i dwoma fungicydami (difenokonazol i drazoxolon) przeprowadzono badania dokowania molekularnego za pomocą programów SwissDock i PatchDock. Oba programy dokowania molekularnego przewidują, że wszystkie badane pestycydy wiążą się z miejscami aktywnymi chitynaz, wytwarzanych przez drobnoustroje glebowe. Istnieją korelacje dla przewidywanych wartości energii wiązania kompleksów receptor-ligand uzyskanych za pomocą dwóch programów, potwierdzając przewidywane interakcje między chitynazami a pestycydami. Oddziaływania chitynaz z pestycydami dotyczą tych samych reszt, jak ich interakcje ze znanymi inhibitorami, co sugeruje hamujące zdolności pestycydów. Pestycydy oddziałują silniej z chitynazami należącymi do rodziny GH18 - ich miejsca aktywne wykazują wyższą polarność niż te z chitynaz GH19. Ponadto, herbicydy wykazują wyższe zdolności hamujące wobec chitynaz bakteryjnych w porównaniu do fungicydów.

5

Investigation of interactions between dermorphin analogs and µ-opioid receptor

Karczyńska A., Zaborowski B., Ślusarz M.

TASK Quarterly : scientific bulletin of Academic Computer Centre in Gdansk

|

2014

|

Vol. 18, No 4

331--336

EN

Opioid receptors play the pain control function in the body. Most of the research is carried out to find the most effective analgesic. The earliest analgesic i s morphine, however, unfortunately it has many side effects [Mizoguchi H et al. 2003 J. Pharmacol Sci. 93 423]. At a later time dermorphin was discovered as another potent analgesic [Mont ecucchi P C et al. 1981 Int. J. Pept. Protein Res. 17 275]. Unfortunately, this peptide is not resistant to enzymatic metabolism [Kisara K et al. 1986 Br. J. Pharmacol. 87 183; Sasaki Y et al. 1985 Neuropeptides 5 391]. The objective of this study is to search for new opioid analgesics by in vestigation of interactions between dermorphin analogs and the μ -opioid receptor using molecular modeling methods. MOPR ( μ -Opioid Peptide Receptor) complexes with several ligands (with kno wn biological activity) were modeled to explain how the structure of the complex was related to the biological activity. The investigated dermorphin analogs containing [ DMT 1 , D -Arg 2 ] (especially tetrapeptides) may become a good alternative for the currently used an algesics.

6

Coarse-grained modeling of protein structure, dynamics and protein-protein interactions

Koliński A., Kmiecik S., Jamróz M., Błaszczyk M., Kouza M., Kurciński M.

TASK Quarterly : scientific bulletin of Academic Computer Centre in Gdansk

|

2014

|

Vol. 18, No 3

219--229

EN

Theoretical prediction of protein structures and dynamics is essent ial for understanding the molecular basis of drug action, metabolic and signaling pathway s in living cells, designing new technologies in the life science and material sciences . We developed and validated a novel multiscale methodology for the study of protein folding proces ses including flexible docking of proteins and peptides. The new modeling technique starts fr om coarse-grained large-scale simulations, followed by selection of the most plausible final structu res and intermediates and, finally, by an all-atom rectification of the obtained structures. Except f or the most basic bioinformatics tools, the entire computational methodology is based on the models an d algorithms developed in our lab. The coarse-grained simulations are based on a high-resol ution lattice representation of protein structures, a knowledge based statistical for ce field and efficient Monte Carlo dynamics schemes, including Replica Exchange algorithms. This p aper focuses on the description of the coarse-grained CABS model and its selected applications.

7

Experimental and theoretical investigation of drotaverine binding to bovine serum albumin

Gałęcki K, Courtade G, McFall A., Prieschl Teixeira R., Grgic M., Esteve-Sistere M., Maglemose Westphalen R., Kowalska-Baron A.

Biotechnology and Food Science

|

2013

|

Vol. 77, nr 1

25--36

EN

This study was motivated by the need to provide more insight into the possible mechanism of the intermolecular interactions between antispasmodic drug drotaverine and one of the serum albumins (BSA), with the aim to indicate the most probable sites of these interactions. For this purpose both experimental (spectrofluorometric titration at various temperatures) and theoretical (molecular mechanics) methods have been applied. The obtained results clearly showed that drotaverine quenched BSA fluorescence, and the most probable mechanism is static quenching. The negative value of the theoretically predicted binding free Gibbs energy (-23.8 kJ/mol) confirmed the existence of the intermolecular interactions involving drotaverine and one tryptophan within BSA protein and was well agreed with the experimentally determined value of -25.2 kJ/mol.

8

Dwupoziomowy model interakcji białko-ligand w dokowaniu molekularnym

Pacholczyk M., Starosolski Z.

Zeszyty Naukowe. Automatyka / Politechnika Śląska

|

2008

|

z. 151

223-232

PL

W pracy przedstawiono ideę dwupoziomowego modelu interakcji białko-ligand w problemie dokowania molekularnego. Dokowanie molekularne może być rozpatrywane jako potencjalna metoda komputerowego wspomagania projektowania i optymalizacji działania nowych leków. Stosowana metoda symulacji, z wykorzystaniem map stochastycznych, wywodząca się z losowych metod planowania trajektorii w robotyce, może być uważana za niezwykle interesujące, nowe podejście do efektywnego próbkowania przestrzeni konformacyjnej ligandu wokół białka. Oddziaływanie białko-ligand podzielone jest na dwie części - elektrostatykę modelowaną za pomocą równania Poissona-Boltzmanna oraz oddziaływania van der Waalsa reprezentowane przez potencjał Lennarda-Jonesa. Mapa stochastyczna w połączeniu z geometrycznym modelem interakcji białko-ligand, takim jak LUDI, może dać pełny obraz procesu dokowania molekularnego, począwszy od fazy niezwiązanej, na fazie końcowej, gdy ligand wiązany jest specyficznymi dla miejsca wiążącego oddziaływaniami, skończywszy.

EN

. In the paper we present an idea of two-level model of protein-ligand interaction for the problem of molecular docking. Molecular docking can be regarded as a potential method for computer aided drug design and optimization. We use stochastic roadmap methodology, inspired by probabilistic path planning in robotics, which can be regarded as a very interesting novel approach to effective sampling of ligand conformational space around a protein molecule. Protein - ligand interaction in divided into two parts electrostatics, modeled by the Poisson-Boltzmann equation, and van der Waals interaction represented by the Lennard-Jones potential. The stochastic roadmap combined with geometrical model of protein - ligand interaction, such as LUDI, could give full insight into the molecular docking problem from unbound phase to the final phase when a ligand is bound to the binding site of a protein.

9

Algorytm haszowania geometrycznego w dokowaniu molekularnym

Pacholczyk M., Bereska D.

Zeszyty Naukowe. Automatyka / Politechnika Śląska

|

2006

|

z. 145

157-162

PL

W pracy przedstawiono implementację oraz wstępne wyniki działania zmodyfikowanego algorytmu wizji komputerowej - haszowania geometrycznego zastosowanego w problemie dokowania molekularnego. Dokowanie molekularne w ujęciu przedstawionym w pracy jest problemem znalezienia najlepszego dopasowania struktury przestrzennej białka oraz mniejszej molekuły - ligandu (molekuły lekopodobnej). Jako model interakcji białko ligand zastosowano powierzchnie interakcji - stanowiących geometryczną reprezentację zbioru reguł rządzących oddziaływaniami na poziomie molekularnym (wiązania wodorowe, oddziaływania hydrofobowe). Właściwości algorytmu zostały sprawdzone podczas próby rekonstrukcji naturalnego dopasowania struktury izomerazy oraz ligandu SO4, pochodzących z kompleksu o oznaczeniu 5TIM (PDB).

EN

The paper presents an implementation and preliminary results obtained with modified computer vision algorithm called geometric hashing applied to the problem of molecular docking. Molecular docking as presented here is the problem of finding the best possible matching between protein structure and a ligand (typically a smaller, drag like molecule). As a model for protein - ligand interaction we use the interaction surfaces - geometric representation of rules governing intramolecular interactions (hydrogen bonds, hydrofobic interactions). We tested our method trying to reconstruct native binding pose of the SO4 ligand and isomerase in 5TIM (PDB) complex.