LIVIVO - Search results -

Search results

Result 1 - 10 of total 412

Search options

Article ; Online: The Future of Medicinal Chemistry, PROTAC, and Undruggable Drug Targets.

Poso, Antti

2021 Volume 64, Issue 15, Page(s) 10680–10681

Abstract: WRD5 is a promising target for anticancer drug discovery. In addition, it plays a vital role in epigenetic regulation. Since biological inactivation of WRD5 is difficult to reach via classical approach, PROTACs (Proteolysis Targeting Chimeras) are ... ...

Abstract	WRD5 is a promising target for anticancer drug discovery. In addition, it plays a vital role in epigenetic regulation. Since biological inactivation of WRD5 is difficult to reach via classical approach, PROTACs (Proteolysis Targeting Chimeras) are offering a new option. In a study, published in this journal, new WRD5 targeting PROTACS are introduced. These new compounds, which are also active in cells, make it possible to evaluate the value of WRD5 as a drug target.
MeSH term(s)	Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacology ; Biphenyl Compounds/chemistry ; Biphenyl Compounds/pharmacology ; Chemistry, Pharmaceutical ; Dihydropyridines/chemistry ; Dihydropyridines/pharmacology ; Dose-Response Relationship, Drug ; Humans ; Intracellular Signaling Peptides and Proteins/antagonists & inhibitors ; Intracellular Signaling Peptides and Proteins/metabolism ; Molecular Structure ; Proteolysis/drug effects ; Structure-Activity Relationship
Chemical Substances	Antineoplastic Agents ; Biphenyl Compounds ; Dihydropyridines ; Intracellular Signaling Peptides and Proteins ; OICR-9429 ; WDR5 protein, human
Language	English
Publishing date	2021-07-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	218133-2
ISSN	1520-4804 ; 0022-2623
ISSN (online)	1520-4804
ISSN	0022-2623
DOI	10.1021/acs.jmedchem.1c01126
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.B 151: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MB 1: Show issues

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.

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Virtual Screening Assisted Search for Inhibitors of the Translocated Intimin Receptor of Enteropathogenic Escherichia Coli.

Pylkkö, Tuomas / Tomašič, Tihomir / Poso, Antti / Tammela, Päivi

Chembiochem : a European journal of chemical biology

2023 Volume 25, Issue 2, Page(s) e202300638

Abstract: This study aimed to identify inhibitors of the translocated intimin receptor (Tir) of enteropathogenic Escherichia coli (EPEC). EPEC is an intestinal pathogen that causes diarrhea and is a major health concern worldwide. Because Tir is a key virulence ... ...

Abstract	This study aimed to identify inhibitors of the translocated intimin receptor (Tir) of enteropathogenic Escherichia coli (EPEC). EPEC is an intestinal pathogen that causes diarrhea and is a major health concern worldwide. Because Tir is a key virulence factor involved in EPEC pathogenesis, inhibiting its function is a potential strategy for controlling EPEC infections. Virtual screening was applied to chemical libraries to search for compounds that inhibit Tir-mediated bacterial adherence to host cells. Three sites were targeted using the cocrystal structure published earlier. A selection of compounds was then assessed in a cell-based infection model and fluorescence microscopy assay. The results of this study provide a basis for further optimization and testing of Tir inhibitors as potential therapeutic agents for EPEC infections.
MeSH term(s)	Humans ; Enteropathogenic Escherichia coli/metabolism ; Adhesins, Bacterial/metabolism ; Escherichia coli Proteins/metabolism ; Receptors, Cell Surface/chemistry ; Carrier Proteins ; Escherichia coli Infections/microbiology
Chemical Substances	Adhesins, Bacterial ; Escherichia coli Proteins ; Receptors, Cell Surface ; Carrier Proteins
Language	English
Publishing date	2023-11-27
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2020469-3
ISSN	1439-7633 ; 1439-4227
ISSN (online)	1439-7633
ISSN	1439-4227
DOI	10.1002/cbic.202300638
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Spatio-temporal evolution of heat waves severity and expansion across the Iberian Peninsula and Balearic islands.

Díaz-Poso, Alejandro / Lorenzo, Nieves / Royé, Dominic

Environmental research

2022 Volume 217, Page(s) 114864

Abstract: In the current climate change scenario, heat waves have become one of the most concerning extreme climatic events, both because of their implications for human health and the economy, and because of their increase in intensity and frequency in recent ... ...

Abstract	In the current climate change scenario, heat waves have become one of the most concerning extreme climatic events, both because of their implications for human health and the economy, and because of their increase in intensity and frequency in recent decades. This work presents for the first time a climatological analysis of heat waves in the Iberian Peninsula and Balearic Archipelago (IPB) using the Excess Heat Factor index (EHF). This index considers the factor of intensity and the acclimatization process of human body in the study of heat waves. We focused on the intensity (also called severity), duration, frequency and spatial extension of heat waves in the IPB in the 1950-2020 period. The exceptional heat wave of August 2018 was approached in a similar way to further explore the usefulness of the EHF index. We found that the EHF index identified heat wave conditions 2 days earlier than indices that used only maximum temperatures. Results showed a significant increase in intensity, duration, frequency and spatial extension of heat waves for the whole IPB for 1950-2020 period. The average extent of heat waves increased by 4.0% per decade and the maximum extent by 4.1% per decade. This trend suggested a significant increase in human exposure, droughts, fire risk and energy demand in this region in the last decades.
MeSH term(s)	Humans ; Spain ; Hot Temperature ; Europe ; Temperature ; Acclimatization ; Climate Change
Language	English
Publishing date	2022-11-19
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	205699-9
ISSN	1096-0953 ; 0013-9351
ISSN (online)	1096-0953
ISSN	0013-9351
DOI	10.1016/j.envres.2022.114864
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 726: 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: Structure of POPC Lipid Bilayers in OPLS3e Force Field.

Kurki, Milla / Poso, Antti / Bartos, Piia / Miettinen, Markus S

Journal of chemical information and modeling

2022

Abstract: It is crucial for molecular dynamics simulations of biomembranes that the force field parameters give a realistic model of the membrane behavior. In this study, we examined the OPLS3e force field for the carbon-hydrogen order ... ...

Abstract	It is crucial for molecular dynamics simulations of biomembranes that the force field parameters give a realistic model of the membrane behavior. In this study, we examined the OPLS3e force field for the carbon-hydrogen order parameters
Language	English
Publishing date	2022-08-31
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.2c00395
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: Structural Characterization of LsrK as a Quorum Sensing Target and a Comparison between X-ray and Homology Models.

Medarametla, Prasanthi / Kronenberger, Thales / Laitinen, Tuomo / Poso, Antti

Journal of chemical information and modeling

2021 Volume 61, Issue 3, Page(s) 1346–1353

Abstract: Quorum sensing is being investigated as an alternative therapeutic strategy in antibacterial drug discovery programs aimed at combatting bacterial resistance. LsrK is an autoinducer-2 kinase (belongs to the sugar kinase family), playing a key role in the ...

Abstract	Quorum sensing is being investigated as an alternative therapeutic strategy in antibacterial drug discovery programs aimed at combatting bacterial resistance. LsrK is an autoinducer-2 kinase (belongs to the sugar kinase family), playing a key role in the phosphorylation of the autoinducer-2 (AI-2) signaling molecules involved in quorum sensing. Inhibiting LsrK could result in reduced pathogenicity by interfering with quorum sensing signaling. Previously, we have generated homology models to employ in structure-based virtual screening and successfully identified the first class of LsrK inhibitors. While conducting these studies, the crystal structure of LsrK was released, providing us with an opportunity to evaluate the reliability and quality of our models. A comparative structural analysis of the crystal structure and homology models revealed consistencies among them in the overall structural fold and binding site. Furthermore, the binding characteristics and conformational changes of LsrK have been investigated using molecular dynamics to inspect whether LsrK undergoes similar conformational changes as that of sugar kinases. These studies revealed the flexibility of the LsrK C-terminal domain (Domain II) attributing to the conformational changes in LsrK resulting in open and closed states during the phosphorylation. Further, simulations provided us with insights into the flexibility of a loop in Domain I that can influence the ligand accessibility to the LsrK binding site.
Language	English
Publishing date	2021-03-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	190019-5
ISSN	1549-960X ; 0095-2338
ISSN (online)	1549-960X
ISSN	0095-2338
DOI	10.1021/acs.jcim.0c01233
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: Machine Learning-Boosted Docking Enables the Efficient Structure-Based Virtual Screening of Giga-Scale Enumerated Chemical Libraries.

Sivula, Toni / Yetukuri, Laxman / Kalliokoski, Tuomo / Käsnänen, Heikki / Poso, Antti / Pöhner, Ina

Journal of chemical information and modeling

2023 Volume 63, Issue 18, Page(s) 5773–5783

Abstract: The emergence of ultra-large screening libraries, filled to the brim with billions of readily available compounds, poses a growing challenge for docking-based virtual screening. Machine learning (ML)-boosted strategies like the tool HASTEN combine rapid ... ...

Abstract	The emergence of ultra-large screening libraries, filled to the brim with billions of readily available compounds, poses a growing challenge for docking-based virtual screening. Machine learning (ML)-boosted strategies like the tool HASTEN combine rapid ML prediction with the brute-force docking of small fractions of such libraries to increase screening throughput and take on giga-scale libraries. In our case study of an anti-bacterial chaperone and an anti-viral kinase, we first generated a brute-force docking baseline for 1.56 billion compounds in the Enamine REAL lead-like library with the fast Glide high-throughput virtual screening protocol. With HASTEN, we observed robust recall of 90% of the true 1000 top-scoring virtual hits in both targets when docking only 1% of the entire library. This reduction of the required docking experiments by 99% significantly shortens the screening time. In the kinase target, the employment of a hydrogen bonding constraint resulted in a major proportion of unsuccessful docking attempts and hampered ML predictions. We demonstrate the optimization potential in the treatment of failed compounds when performing ML-boosted screening and benchmark and showcase HASTEN as a fast and robust tool in a growing arsenal of approaches to unlock the chemical space covered by giga-scale screening libraries for everyday drug discovery campaigns.
MeSH term(s)	Small Molecule Libraries/pharmacology ; High-Throughput Screening Assays ; Antiviral Agents ; Benchmarking ; Machine Learning
Chemical Substances	Small Molecule Libraries ; Antiviral Agents
Language	English
Publishing date	2023-09-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	190019-5
ISSN	1549-960X ; 0095-2338
ISSN (online)	1549-960X
ISSN	0095-2338
DOI	10.1021/acs.jcim.3c01239
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: Binding Affinity via Docking: Fact and Fiction.

Pantsar, Tatu / Poso, Antti

Molecules (Basel, Switzerland)

2018 Volume 23, Issue 8

Abstract: In 1982, Kuntz et al. published an article with the title "A Geometric Approach to Macromolecule-Ligand Interactions", where they described a method "to explore geometrically feasible alignment of ligands and receptors of known structure". Since then, ... ...

Abstract	In 1982, Kuntz et al. published an article with the title "A Geometric Approach to Macromolecule-Ligand Interactions", where they described a method "to explore geometrically feasible alignment of ligands and receptors of known structure". Since then, small molecule docking has been employed as a fast way to estimate the binding pose of a given compound within a specific target protein and also to predict binding affinity. Remarkably, the first docking method suggested by Kuntz and colleagues aimed to predict binding poses but very little was specified about binding affinity. This raises the question as to whether docking is the right tool to estimate binding affinity. The short answer is no, and this has been concluded in several comprehensive analyses. However, in this opinion paper we discuss several critical aspects that need to be reconsidered before a reliable binding affinity prediction through docking is realistic. These are not the only issues that need to be considered, but they are perhaps the most critical ones. We also consider that in spite of the huge efforts to enhance scoring functions, the accuracy of binding affinity predictions is perhaps only as good as it was 10⁻20 years ago. There are several underlying reasons for this poor performance and these are analyzed. In particular, we focus on the role of the solvent (water), the poor description of H-bonding and the lack of the systems' true dynamics. We hope to provide readers with potential insights and tools to overcome the challenging issues related to binding affinity prediction via docking.
MeSH term(s)	Binding Sites ; Databases, Protein ; Hydrogen Bonding ; Hydrophobic and Hydrophilic Interactions ; Ligands ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; Protein Binding ; Protein Conformation ; Proteins/chemistry ; Software ; Solvents/chemistry ; Static Electricity ; Thermodynamics ; Water/chemistry
Chemical Substances	Ligands ; Proteins ; Solvents ; Water (059QF0KO0R)
Language	English
Publishing date	2018-07-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules23081899
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.MO 81: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: The autoinhibited state of MKK4: Phosphorylation, putative dimerization and R134W mutant studied by molecular dynamics simulations.

Shevchenko, Ekaterina / Poso, Antti / Pantsar, Tatu

Computational and structural biotechnology journal

2020 Volume 18, Page(s) 2687–2698

Abstract: Protein kinases are crucial components of the cell-signalling machinery that orchestrate and convey messages to their downstream targets. Most often, kinases are activated upon a phosphorylation to their activation loop, which will shift the kinase into ... ...

Abstract	Protein kinases are crucial components of the cell-signalling machinery that orchestrate and convey messages to their downstream targets. Most often, kinases are activated upon a phosphorylation to their activation loop, which will shift the kinase into the active conformation. The Dual specificity mitogen-activated protein kinase kinase 4 (MKK4) exists in a unique conformation in its inactive unphosphorylated state, where its activation segment appears in a stable α-helical conformation. However, the precise role of this unique conformational state of MKK4 is unknown. Here, by all-atom molecular dynamics simulations (MD simulations), we show that this inactive state is unstable as monomer even when unphosphorylated and that the phosphorylation of the activation segment further destabilizes the autoinhibited α-helix. The specific phosphorylation pattern of the activation segment has also a unique influence on MKK4 dynamics. Furthermore, we observed that this specific inactive state is stable as a dimer, which becomes destabilized upon phosphorylation. Finally, we noticed that the most frequent MKK4 mutation observed in cancer, R134W, which role has not been disclosed to date, contributes to the dimer stability. Based on these data we postulate that MKK4 occurs as a dimer in its inactive autoinhibited state, providing an additional layer for its activity regulation.
Language	English
Publishing date	2020-09-20
Publishing country	Netherlands
Document type	Journal Article
ISSN	2001-0370
ISSN	2001-0370
DOI	10.1016/j.csbj.2020.09.017
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

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.

Details ▾
- Full text online
- Order with fees

Article ; Online: Virus structure and structure-based antivirals.

Plavec, Zlatka / Pöhner, Ina / Poso, Antti / Butcher, Sarah J

Current opinion in virology

2021 Volume 51, Page(s) 16–24

Abstract: Structure-based antiviral developments in the past two years have been dominated by the structure determination and inhibition of SARS-CoV-2 proteins and new lead molecules for picornaviruses. The SARS-CoV-2 spike protein has been targeted successfully ... ...

Abstract	Structure-based antiviral developments in the past two years have been dominated by the structure determination and inhibition of SARS-CoV-2 proteins and new lead molecules for picornaviruses. The SARS-CoV-2 spike protein has been targeted successfully with antibodies, nanobodies, and receptor protein mimics effectively blocking receptor binding or fusion. The two most promising non-structural proteins sharing strong structural and functional conservation across virus families are the main protease and the RNA-dependent RNA polymerase, for which design and reuse of broad range inhibitors already approved for use has been an attractive avenue. For picornaviruses, the increasing recognition of the transient expansion of the capsid as a critical transition towards RNA release has been targeted through a newly identified, apparently widely conserved, druggable, interprotomer pocket preventing viral entry. We summarize some of the key papers in these areas and ponder the practical uses and contributions of molecular modeling alongside empirical structure determination.
MeSH term(s)	Animals ; Antiviral Agents/chemistry ; Antiviral Agents/pharmacology ; COVID-19/drug therapy ; Drug Delivery Systems ; Drug Design ; Drug Repositioning ; Humans ; Picornaviridae/chemistry ; Picornaviridae/enzymology ; SARS-CoV-2/chemistry ; SARS-CoV-2/enzymology
Chemical Substances	Antiviral Agents
Language	English
Publishing date	2021-09-24
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2611378-8
ISSN	1879-6265 ; 1879-6257
ISSN (online)	1879-6265
ISSN	1879-6257
DOI	10.1016/j.coviro.2021.09.005
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Inhibitor induced conformational changes in SARS-COV-2 papain-like protease.

Ferreira, Glaucio Monteiro / Pillaiyar, Thanigaimalai / Hirata, Mario Hiroyuki / Poso, Antti / Kronenberger, Thales

Scientific reports

2022 Volume 12, Issue 1, Page(s) 11585

Abstract: SARS-CoV-2's papain-like protease ( ... ...

Abstract	SARS-CoV-2's papain-like protease (PL
MeSH term(s)	Aniline Compounds ; Antiviral Agents/pharmacology ; Benzamides ; COVID-19/drug therapy ; Coronavirus Papain-Like Proteases ; Humans ; Ligands ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; Naphthalenes ; Protease Inhibitors/chemistry ; Protease Inhibitors/pharmacology ; SARS-CoV-2
Chemical Substances	5-amino-2-methyl-N-((R)-1-(1-naphthyl)ethyl)benzamide ; Aniline Compounds ; Antiviral Agents ; Benzamides ; Ligands ; Naphthalenes ; Protease Inhibitors ; Coronavirus Papain-Like Proteases (EC 3.4.22.2) ; papain-like protease, SARS-CoV-2 (EC 3.4.22.2)
Language	English
Publishing date	2022-07-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-15181-y
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

To top

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito