A5080257017- Receptor Mechanisms and Signaling
- Protein Structure and Dynamics
- Cannabis and Cannabinoid Research
- Mass Spectrometry Techniques and Applications
- Synthesis and Reactions of Organic Compounds
- Alzheimer's disease research and treatments
- Lipid Membrane Structure and Behavior
- Computational Drug Discovery Methods
- Neuropeptides and Animal Physiology
- Cyclopropane Reaction Mechanisms
- Pancreatic function and diabetes
- Synthesis of heterocyclic compounds
- Synthesis and Reactivity of Sulfur-Containing Compounds
- Fluorine in Organic Chemistry
- DNA and Nucleic Acid Chemistry
- Monoclonal and Polyclonal Antibodies Research
- Pharmacological Receptor Mechanisms and Effects
- Photoreceptor and optogenetics research
- Diabetes Treatment and Management
- Neurotransmitter Receptor Influence on Behavior
- Supramolecular Self-Assembly in Materials
- Drug Transport and Resistance Mechanisms
- Trypanosoma species research and implications
- Renal and related cancers
- Biochemical and Molecular Research
University of Warsaw
2016-2025
Vanderbilt University
2008
Polish Academy of Sciences
2008
Institute of Organic Chemistry
2008
G protein-coupled receptors (GPCRs) constitute a functionally diverse protein family and are targets for broad spectrum of pharmaceuticals. Technological progress in X-ray crystallography cryogenic electron microscopy has enabled extensive, high-resolution structural characterisation GPCRs different conformational states. However, as highly dynamic events underlie GPCR signalling, complete understanding functionality requires insights into their dynamics. Here, we present large dataset...
Nitrones derived from aromatic or aliphatic aldehydes ketones react with hexafluoropropene (HFP) 2H-pentafluoropropene (PFP) to give the respective fluorinated isoxazolidine derivatives in good yields complete regioselectivity and moderate diastereoselectivity. Catalytic hydrogenolysis of N−O bond under ambient pressure temperature leads fluorides β-amino acids that undergo cyclization α-trifluoromethylated β-lactams or, acidic conditions, form esters acids.
Due to the involvement of G protein-coupled receptors (GPCRs) in most physiological and pathological processes humans they have been attracting a lot attention from pharmaceutical industry as well scientific community. Therefore, need for new, high quality structures GPCRs is enormous. The updated homology modeling service GPCRM (http://gpcrm.biomodellab.eu/) meets those expectations by greatly reducing execution time submissions (from days hours/minutes) with nearly same average obtained...
The CB1 cannabinoid receptor (CB1R) contains one of the longest N termini among class A G protein-coupled receptors. Mutagenesis studies suggest that allosteric binding site cannabidiol (CBD) involves residues from terminal domain. In order to study CBD CB1R we modeled whole N-terminus this using replica exchange molecular dynamics with solute tempering (REST2) approach. Then, obtained structures terminus were used for ligand docking. natural agonist, Δ9-THC, was docked orthosteric and a...
It has been reported that some hydrophobic ligands of G-protein-coupled receptors access the receptor's binding site from membrane rather than bulk water. In order to identify most probable ligand entrance pathway into CB1 receptor, we performed several steered molecular dynamics (SMD) simulations two agonists, THC and anandamide, pulling them with constant velocity. The four main directions were probed: between helices TM4 TM5, TM5 TM6, TM7 TM1/TM2, toward smallest forces measured during...
Alzheimer’s disease (AD) is the leading cause of dementia and characterized by a presence amyloid plaques, composed mostly amyloid-β (Aβ) peptides, in brains AD patients. The peptides are generated from precursor protein (APP), which undergoes sequence cleavages, referred as trimming, performed γ-secretase. Here, we investigated conformational changes series β-amyloid substrates (from less more amyloidogenic pathways) active site presenilin-1, catalytic subunit trimmed every three residues,...
Most G protein-coupled receptors that bind the hydrophobic ligands (lipid and steroid receptors) belong to most populated class A (rhodopsin-like) of these receptors. Typical examples lipid are: rhodopsin, cannabinoid (CB), sphingosine-1-phosphate (S1P) lysophosphatidic (LPA) The access receptor binding site from bilayer not only because their low solubility in water but also a large N-terminal domain plug preventing orthosteric extracellular milieu. In order identify probable ligand exit...
Alzheimer's disease is the most common progressive neurodegenerative disorder and characterized by presence of amyloid β (Aβ) plaques in brain. The γ-secretase complex, which produces Aβ, an intramembrane-cleaving protease consisting four membrane proteins. In this paper we investigated amyloidogenic fragments precursor protein (substrates Aβ43 Aβ45, leading to less Aβ40 more Aβ42, respectively) docked binding site presenilin, catalytic subunit γ-secretase. total, performed 9 μs all-atom...
GPCRsignal (https://gpcrsignal.biomodellab.eu/) is a webserver devoted to signaling complexes of G-protein-coupled receptors (GPCRs). The recent improvement in cryo-electron microscopy resulted the determination large number high-resolution structures GPCRs bound their effector proteins: G proteins or arrestins. Analyzing interfaces between receptor and an protein high importance since selection proper specific conformation arrestin leads changes that can significantly affect action drugs....
Abstract Despite recent advances in research, the mechanism of Alzheimer's disease is not fully understood yet. Understanding process cleavage and then trimming peptide substrates, can help selectively block γ-secretase (GS) to stop overproduction amyloidogenic products. Our GS-SMD server (https://gs-smd.biomodellab.eu/) allows cleaving unfolding all currently known GS substrates (more than 170 substrates). The substrate structure obtained by threading sequence into complex. simulations are...
Abstract ChemInform is a weekly Abstracting Service, delivering concise information at glance that was extracted from about 200 leading journals. To access of an article which published elsewhere, please select “Full Text” option. The original trackable via the “References”
Abstract ChemInform is a weekly Abstracting Service, delivering concise information at glance that was extracted from about 200 leading journals. To access of an article which published elsewhere, please select “Full Text” option. The original trackable via the “References”