LIVIVO - Search results -

Search results

Result 1 - 10 of total 13

Search options

Article: Understanding the Dynamics of the Structural States of Cannabinoid Receptors and the Role of Different Modulators.

Manandhar, Anjela / Haron, Mona H / Klein, Michael L / Elokely, Khaled

2022 Volume 12, Issue 12

Abstract: The cannabinoid receptors ... ...

Abstract	The cannabinoid receptors CB
Language	English
Publishing date	2022-12-18
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662250-6
ISSN	2075-1729
ISSN	2075-1729
DOI	10.3390/life12122137
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Article ; Online: Sequence Dependence in Nucleosome Dynamics.

Khatua, Prabir / Tang, Phu K / Ghosh Moulick, Abhik / Patel, Rutika / Manandhar, Anjela / Loverde, Sharon M

The journal of physical chemistry. B

2024 Volume 128, Issue 13, Page(s) 3090–3101

Abstract: The basic packaging unit of eukaryotic chromatin is the nucleosome that contains 145-147 base pair duplex DNA wrapped around an octameric histone protein. While the DNA sequence plays a crucial role in controlling the positioning of the nucleosome, the ... ...

Abstract	The basic packaging unit of eukaryotic chromatin is the nucleosome that contains 145-147 base pair duplex DNA wrapped around an octameric histone protein. While the DNA sequence plays a crucial role in controlling the positioning of the nucleosome, the molecular details behind the interplay between DNA sequence and nucleosome dynamics remain relatively unexplored. This study analyzes this interplay in detail by performing all-atom molecular dynamics simulations of nucleosomes, comparing the human α-satellite palindromic (ASP) and the strong positioning "Widom-601" DNA sequence at time scales of 12 μs. The simulations are performed at salt concentrations 10-20 times higher than physiological salt concentrations to screen the electrostatic interactions and promote unwrapping. These microsecond-long simulations give insight into the molecular-level sequence-dependent events that dictate the pathway of DNA unwrapping. We find that the "ASP" sequence forms a loop around SHL ± 5 for three sets of simulations. Coincident with loop formation is a cooperative increase in contacts with the neighboring N-terminal H2B tail and C-terminal H2A tail and the release of neighboring counterions. We find that the Widom-601 sequence exhibits a strong breathing motion of the nucleic acid ends. Coincident with the breathing motion is the collapse of the full N-terminal H3 tail and formation of an α-helix that interacts with the H3 histone core. We postulate that the dynamics of these histone tails and their modification with post-translational modifications (PTMs) may play a key role in governing this dynamics.
MeSH term(s)	Humans ; Nucleosomes ; Histones/chemistry ; Chromatin ; DNA/chemistry ; Molecular Dynamics Simulation
Chemical Substances	Nucleosomes ; Histones ; Chromatin ; DNA (9007-49-2)
Language	English
Publishing date	2024-03-26
Publishing country	United States
Document type	Journal Article
ISSN	1520-5207
ISSN (online)	1520-5207
DOI	10.1021/acs.jpcb.3c07363
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Potential Pro-Inflammatory Effect of Vitamin E Analogs through Mitigation of Tetrahydrocannabinol (THC) Binding to the Cannabinoid 2 Receptor.

Manandhar, Anjela / Haron, Mona H / Ross, Samir A / Klein, Michael L / Elokely, Khaled M

International journal of molecular sciences

2022 Volume 23, Issue 8

Abstract: Vitamin E acetate, which is used as a diluent of tetrahydrocannabinol (THC), has been reported as the primary causative agent of e-cigarette, or vaping, product use-associated lung injury (EVALI). Here, we employ in vitro assays, docking, and molecular ... ...

Abstract	Vitamin E acetate, which is used as a diluent of tetrahydrocannabinol (THC), has been reported as the primary causative agent of e-cigarette, or vaping, product use-associated lung injury (EVALI). Here, we employ in vitro assays, docking, and molecular dynamics (MD) computer simulations to investigate the interaction of vitamin E with the membrane-bound cannabinoid 2 receptor (CB2R), and its role in modulating the binding affinity of THC to CB2R. From the MD simulations, we determined that vitamin E interacts with both CB2R and membrane phospholipids. Notably, the synchronized effect of these interactions likely facilitates vitamin E acting as a lipid modulator for the cannabinoid system. Furthermore, MD simulation and trajectory analysis show that when THC binds to CB2R in the presence of vitamin E, the binding cavity widens, facilitating the entry of water molecules into it, leading to a reduced interaction of THC with CB2R. Additionally, the interaction between THC and vitamin E in solution is stabilized by several H bonds, which can directly limit the interaction of free THCs with CB2R. Overall, both the MD simulations and the in vitro dissociation assay results indicate that THC binding to CB2R is reduced in the presence of vitamin E. Our study discusses the role of vitamin E in limiting the effect of THCs and its implications on the reported pathology of EVALI.
MeSH term(s)	Dronabinol/pharmacology ; Electronic Nicotine Delivery Systems ; Genetic Diseases, X-Linked ; Receptors, Cannabinoid ; Thrombocytopenia ; Vaping ; Vitamin E/pharmacology
Chemical Substances	Receptors, Cannabinoid ; Vitamin E (1406-18-4) ; Dronabinol (7J8897W37S)
Language	English
Publishing date	2022-04-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23084291
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Potential Pro-Inflammatory Effect of Vitamin E Analogs through Mitigation of Tetrahydrocannabinol (THC) Binding to the Cannabinoid 2 Receptor

Anjela Manandhar / Mona H. Haron / Samir A. Ross / Michael L. Klein / Khaled M. Elokely

International Journal of Molecular Sciences, Vol 23, Iss 4291, p

2022 Volume 4291

Abstract	Vitamin E acetate, which is used as a diluent of tetrahydrocannabinol (THC), has been reported as the primary causative agent of e-cigarette, or vaping, product use-associated lung injury (EVALI). Here, we employ in vitro assays, docking, and molecular dynamics (MD) computer simulations to investigate the interaction of vitamin E with the membrane-bound cannabinoid 2 receptor (CB2R), and its role in modulating the binding affinity of THC to CB2R. From the MD simulations, we determined that vitamin E interacts with both CB2R and membrane phospholipids. Notably, the synchronized effect of these interactions likely facilitates vitamin E acting as a lipid modulator for the cannabinoid system. Furthermore, MD simulation and trajectory analysis show that when THC binds to CB2R in the presence of vitamin E, the binding cavity widens, facilitating the entry of water molecules into it, leading to a reduced interaction of THC with CB2R. Additionally, the interaction between THC and vitamin E in solution is stabilized by several H bonds, which can directly limit the interaction of free THCs with CB2R. Overall, both the MD simulations and the in vitro dissociation assay results indicate that THC binding to CB2R is reduced in the presence of vitamin E. Our study discusses the role of vitamin E in limiting the effect of THCs and its implications on the reported pathology of EVALI.
Keywords	EVALI ; THC ; CB2R ; MD simulation ; inflammatory ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Targeting SARS-CoV-2 M3CLpro by HCV NS3/4a Inhibitors:

Manandhar, Anjela / Blass, Benjamin E / Colussi, Dennis J / Almi, Imane / Abou-Gharbia, Magid / Klein, Michael L / Elokely, Khaled M

Journal of chemical information and modeling

2021 Volume 61, Issue 2, Page(s) 1020–1032

Abstract: Currently the entire human population is in the midst of a global pandemic caused by SARS-CoV-2 ( ...

Abstract	Currently the entire human population is in the midst of a global pandemic caused by SARS-CoV-2 (
MeSH term(s)	Antiviral Agents/pharmacology ; Computer Simulation ; Crystallography, X-Ray ; Cysteine Proteases/chemistry ; Cysteine Proteases/drug effects ; Humans ; In Vitro Techniques ; Microbial Sensitivity Tests ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; Protein Conformation ; SARS-CoV-2/drug effects ; SARS-CoV-2/enzymology ; Serine Proteases ; Serine Proteinase Inhibitors/pharmacology ; Viral Nonstructural Proteins/antagonists & inhibitors
Chemical Substances	Antiviral Agents ; Serine Proteinase Inhibitors ; Viral Nonstructural Proteins ; Cysteine Proteases (EC 3.4.-) ; NS3-4A serine protease, Hepatitis C virus (EC 3.4.-) ; Serine Proteases (EC 3.4.-)
Language	English
Publishing date	2021-02-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	190019-5
ISSN	1549-960X ; 0095-2338
ISSN (online)	1549-960X
ISSN	0095-2338
DOI	10.1021/acs.jcim.0c01457
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1230: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: The Interaction of Supramolecular Anticancer Drug Amphiphiles with Phospholipid Membranes.

Tang, Phu K / Manandhar, Anjela / Hu, William / Kang, Myungshim / Loverde, Sharon M

Nanoscale advances

2020 Volume 3, Issue 2, Page(s) 370–382

Abstract: The shape of drug delivery vehicles impacts both the circulation time and the effectiveness of the vehicle. Peptide-based drug amphiphiles (DAs) are promising new candidates as drug delivery vehicles that can self-assemble into shapes such as ... ...

Abstract	The shape of drug delivery vehicles impacts both the circulation time and the effectiveness of the vehicle. Peptide-based drug amphiphiles (DAs) are promising new candidates as drug delivery vehicles that can self-assemble into shapes such as nanofilament and nanotube (diameter ~ 6-10 nm). The number of conjugated drugs affects the IC50 of these DAs, which is correlated to the effective cellular uptake. Characterizing and optimizing the interaction of these DAs and their assemblies with the cellular membrane is experimentally challenging. Long-time molecular dynamics can determine if the DA molecular structure affects the translocation across and interaction with the cellular membrane. Here, we report long-time atomistic simulation on Anton 2 (up to 25 μs) of these DAs with model cellular membranes. Results indicate that the interaction of these DAs with model cellular membranes is dependent on the number of conjugated drugs. We find that, with increased drug loading, the hydrophobic drug (camptothecin) builds up in the outer hydrophobic core of the membrane, pulling in positively charged peptide groups. Next, we computationally probe the interaction of differing shapes of these model drug delivery vehicles-nanofilament and nanotube-with the same model membranes, finding that the interaction of these nanostructures with the membrane is strongly repulsive. Results suggest that the hydrogen bond density between the nanostructure and the membrane may play a key role in modulating the interaction between the nanostructure and the membrane. Taken together, these results offer important insights for the rational design of peptide-based drug delivery vehicles.
Language	English
Publishing date	2020-10-26
Publishing country	England
Document type	Journal Article
ISSN	2516-0230
ISSN (online)	2516-0230
DOI	10.1039/d0na00697a
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Effect of Nucleotide State on the Protofilament Conformation of Tubulin Octamers.

Manandhar, Anjela / Kang, Myungshim / Chakraborty, Kaushik / Loverde, Sharon M

The journal of physical chemistry. B

2018 Volume 122, Issue 23, Page(s) 6164–6178

Abstract: At the molecular level, the dynamic instability (random growth and shrinkage) of the microtubule (MT) is driven by the nucleotide state (GTP vs GDP) in the β subunit of the tubulin dimers at the MT cap. Here, we use large-scale molecular dynamics (MD) ... ...

Abstract	At the molecular level, the dynamic instability (random growth and shrinkage) of the microtubule (MT) is driven by the nucleotide state (GTP vs GDP) in the β subunit of the tubulin dimers at the MT cap. Here, we use large-scale molecular dynamics (MD) simulations and normal-mode analysis (NMA) to characterize the effect of a single GTP cap layer on tubulin octamers composed of two neighboring protofilaments (PFs). We utilize recently reported high-resolution structures of dynamic MTs to simulate a GDP octamer both with and without a single GTP cap layer. We perform multiple replicas of long-time atomistic MD simulations (3 replicas, 0.3 μs for each replica, 0.9 μs for each octamer system, and 1.8 μs total) of both octamers. We observe that a single GTP cap layer induces structural differences in neighboring PFs, finding that one PF possesses a gradual curvature, compared to the second PF which possesses a kinked conformation. This results in either curling or splaying between these PFs. We suggest that this is due to asymmetric strengths of longitudinal contacts between the two PFs. Furthermore, using NMA, we calculate mechanical properties of these octamer systems and find that octamer system with a single GTP cap layer possesses a lower flexural rigidity.
MeSH term(s)	Dimerization ; Guanosine Diphosphate/chemistry ; Guanosine Diphosphate/metabolism ; Guanosine Triphosphate/chemistry ; Guanosine Triphosphate/metabolism ; Microtubules/chemistry ; Molecular Dynamics Simulation ; Protein Conformation ; Tubulin/chemistry ; Tubulin/metabolism
Chemical Substances	Tubulin ; Guanosine Diphosphate (146-91-8) ; Guanosine Triphosphate (86-01-1)
Language	English
Publishing date	2018-06-06
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ISSN	1520-5207
ISSN (online)	1520-5207
DOI	10.1021/acs.jpcb.8b02193
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Discovery of Novel Small-Molecule Inhibitors of SARS-CoV-2 Main Protease as Potential Leads for COVID-19 Treatment.

Manandhar, Anjela / Srinivasulu, Vunnam / Hamad, Mohamad / Tarazi, Hamadeh / Omar, Hany / Colussi, Dennis J / Gordon, John / Childers, Wayne / Klein, Michael L / Al-Tel, Taleb H / Abou-Gharbia, Magid / Elokely, Khaled M

Journal of chemical information and modeling

2021 Volume 61, Issue 9, Page(s) 4745–4757

Abstract: The main protease of SARS-CoV-2 virus, ... ...

Abstract	The main protease of SARS-CoV-2 virus, M
MeSH term(s)	Antiviral Agents/pharmacology ; COVID-19/drug therapy ; Humans ; Molecular Docking Simulation ; Peptide Hydrolases ; Protease Inhibitors/pharmacology ; SARS-CoV-2
Chemical Substances	Antiviral Agents ; Protease Inhibitors ; Peptide Hydrolases (EC 3.4.-)
Language	English
Publishing date	2021-08-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	190019-5
ISSN	1549-960X ; 0095-2338
ISSN (online)	1549-960X
ISSN	0095-2338
DOI	10.1021/acs.jcim.1c00684
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1230: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Rational Coarse-Grained Molecular Dynamics Simulations of Supramolecular Anticancer Nanotubes

Manandhar, Anjela / Chakraborty, Kaushik / Tang, Phu K / Kang, Myungshim / Zhang, Pengcheng / Cui, Honggang / Loverde, Sharon M

Journal of physical chemistry. 2019 Nov. 21, v. 123, no. 50

2019

Abstract: Peptide self-assembly has been used to design an array of nanostructures that possess functional biomedical applications. Experimental studies have reported nanofilament and nanotube formation from peptide-based drug amphiphiles (DAs). These DAs have ... ...

Abstract	Peptide self-assembly has been used to design an array of nanostructures that possess functional biomedical applications. Experimental studies have reported nanofilament and nanotube formation from peptide-based drug amphiphiles (DAs). These DAs have shown to possess an inherently high drug loading with a tunable release mechanism. Herein, we report rational coarse-grained molecular dynamics simulations of the self-assembly process and the structure and stability of preassembled nanotubes at longer timescales (μs). We find that aggregation between these DAs at the submicrosecond timescale is driven by directional aromatic interactions between the drugs. The drugs form a large and high-density nucleus that is stable throughout microsecond timescales. Simulations of nanotubes characterize the drug–drug stacking and find correlations at nanometer length scales. These simulations can inform the rational molecular design of drug amphiphiles.
Keywords	drugs ; molecular dynamics ; nanotubes ; peptides ; simulation models ; surfactants
Language	English
Dates of publication	2019-1121
Size	p. 10582-10593.
Publishing place	American Chemical Society
Document type	Article
ISSN	1520-5207
DOI	10.1021/acs.jpcb.9b07417
Database	NAL-Catalogue (AGRICOLA)

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article: Effect of Nucleotide State on the Protofilament Conformation of Tubulin Octamers

Manandhar, Anjela / Kaushik Chakraborty / Myungshim Kang / Sharon M. Loverde

Journal of physical chemistry. 2018 May 16, v. 122, no. 23

2018

Abstract	At the molecular level, the dynamic instability (random growth and shrinkage) of the microtubule (MT) is driven by the nucleotide state (GTP vs GDP) in the β subunit of the tubulin dimers at the MT cap. Here, we use large-scale molecular dynamics (MD) simulations and normal-mode analysis (NMA) to characterize the effect of a single GTP cap layer on tubulin octamers composed of two neighboring protofilaments (PFs). We utilize recently reported high-resolution structures of dynamic MTs to simulate a GDP octamer both with and without a single GTP cap layer. We perform multiple replicas of long-time atomistic MD simulations (3 replicas, 0.3 μs for each replica, 0.9 μs for each octamer system, and 1.8 μs total) of both octamers. We observe that a single GTP cap layer induces structural differences in neighboring PFs, finding that one PF possesses a gradual curvature, compared to the second PF which possesses a kinked conformation. This results in either curling or splaying between these PFs. We suggest that this is due to asymmetric strengths of longitudinal contacts between the two PFs. Furthermore, using NMA, we calculate mechanical properties of these octamer systems and find that octamer system with a single GTP cap layer possesses a lower flexural rigidity.
Keywords	guanosine diphosphate ; guanosine triphosphate ; mechanical properties ; microtubules ; molecular dynamics ; shrinkage ; tubulin
Language	English
Dates of publication	2018-0516
Size	p. 6164-6178.
Publishing place	American Chemical Society
Document type	Article
ISSN	1520-5207
DOI	10.1021/acs.jpcb.8b02193
Database	NAL-Catalogue (AGRICOLA)

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

To top

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Inter-library loan at ZB MED