A5035862091- Protein Structure and Dynamics
- Receptor Mechanisms and Signaling
- Mass Spectrometry Techniques and Applications
- Neuroendocrine regulation and behavior
- Stress Responses and Cortisol
- Cancer therapeutics and mechanisms
- Lipid Membrane Structure and Behavior
- Neuropeptides and Animal Physiology
- Enzyme Structure and Function
- Memory and Neural Mechanisms
- Synthesis and biological activity
- Photoreceptor and optogenetics research
- Alzheimer's disease research and treatments
- Neuroscience and Neuropharmacology Research
- Crystallization and Solubility Studies
- Crystallography and molecular interactions
- Glycosylation and Glycoproteins Research
- Phenothiazines and Benzothiazines Synthesis and Activities
- X-ray Diffraction in Crystallography
- Analytical Chemistry and Chromatography
- Chemical Synthesis and Analysis
- Force Microscopy Techniques and Applications
- Inhalation and Respiratory Drug Delivery
- Drug Transport and Resistance Mechanisms
- Bioactive Compounds and Antitumor Agents
Mossakowski Medical Research Institute, Polish Academy of Sciences
2014-2024
Polish Academy of Sciences
2014-2024
University Clinical Centre
2023
University of Warsaw
2019-2020
Medical University of Lublin
2011-2013
International Institute of Molecular and Cell Biology
2006-2011
Molecular docking of peptides to proteins can be a useful tool in the exploration possible peptide binding sites and poses. CABS-dock is method for protein-peptide that features significant conformational flexibility both protein molecules during search site. The has been made available as web server standalone package. an easy use with simple interface. package command-line program dedicated professional users. It offers number advanced features, analysis tools support large-sized systems....
The γ-secretase complex has a decisive role in the development of Alzheimer’s disease, that it cleaves precursor to create amyloid β peptide whose aggregates form senile plaques encountered brains patients. Γ-secretase is member intramembrane-cleaving proteases which process their transmembrane substrates within bilayer. Many mutations early onset familial disease are linked presenilin 1, catalytic component γ-secretase, active requires its endoproteolytic cleavage into N-terminal and...
Abstract G‐protein‐coupled receptors (GPCRs) are important targets for treating severe diseases. However why certain molecules act as activators whereas others, with similar structures, block GPCR activation, is poorly understood since the same molecule can activate one receptor subtype while blocking another closely related receptor. To shed light on these central questions, we used all‐atom, long‐time‐scale molecular dynamics simulations κ‐opioid and μ‐opioid (κOR μOR). We found that water...
A novel series of N-acylated ciprofloxacin (CP) conjugates 1-21 were synthesized and screened as potential antimicrobial agents. Conjugates 1 2 1.25-10-fold more potent than CP toward all Staphylococci (minimal inhibitory concentration 0.05-0.4 μg/mL). Most the chloro- (3-7), bromo- (8-11), CF3-alkanoyl (14-16) derivatives expressed higher or comparable activity to against selected Gram-positive strains. few analogues (5, 10, 11) also effective chosen clinical Gram-negative rods. 5, 11...
Bacteriorhodopsin (bR) is a membrane protein found in the archae Halobacterium salinarum. Here, we studied wild type bR and especially triple mutant bR, 3Glu [E9Q/E194Q/E204Q], combination with wide gap semiconductor TiO2 for their suitability as efficient light harvester solar cell. Our differential scanning calorimetry data show thermal robustness of mutant, which make them good candidates photosensitizer cells. Molecular modeling indicates that binding to exposed oxygen atoms anatase...
Single-molecule force spectroscopy (SMFS) is a powerful tool to dissect molecular interactions that govern the stability and function of proteins. We applied SMFS understand effect Zn2+ on underlying structure rhodopsin. Force-distance curves obtained from assays revealed strength location stabilize structural segments within this receptor. The inclusion ZnCl2 in assay buffer increased most segments. This was not mimicked by CaCl2, CdCl2, or CoCl2. Thus, stabilizes rhodopsin specific manner.
Monoclonal antibodies targeting GD2 ganglioside (GD2) have recently been approved for the treatment of high risk neuroblastoma and are extensively evaluated in clinics other indications. This study illustrates how a therapeutic antibody distinguishes between different types gangliosides present on normal cancer cells informs synthetic peptides can imitate its binding to antibody. Using resolution crystal structures we demonstrate that recognition by model (14G2a) is based primarily an...
G-protein-coupled receptors (GPCRs) play key roles in living organisms. Therefore, it is important to determine their functional structures. The second extracellular loop (ECL2) a functionally region of GPCRs, which poses significant challenge for computational structure prediction methods. In this work, we evaluated CABS, well-established protein modeling tool predicting ECL2 13 GPCRs. ECL2s (with between and 34 residues) are predicted an environment other loops being fully flexible the...
The β2 adrenergic receptor (β2-AR) has become a model system for studying the ligand recognition process and mechanism of G protein coupled receptors activation. In present study stereoisomers fenoterol some its derivatives (N = 94 molecules) were used as molecular probes to identify differences in stereo-recognition interactions between β2-AR structurally similar agonists. aimed at determining 3D models derivative-β2-AR complexes. Molecular have been developed by using crystal structure...
One of the reasons for cellular changes in lung tissue exposed to diesel exhaust composed soot particles with adsorbed volatile organic molecules is reduction clearance rate pulmonary region respiratory system. The interaction fractal-like and substances a surfactant monolayer limits its dynamic activity. surface properties Survanta, purified extract bovine (LS), which interacted carbon (200 nm aggregates) benzo[a]pyrene (BaP), were measured oscillating bubble technique. results showed...
The combination of ion mobility mass spectrometry studies and theoretical calculations including docking permitted a detailed structural description noncovalent complexes folic acid (FA) native cyclodextrins (α-CD, β-CD, γ-CD). mode association depended on the cavity size cyclodextrin. structure FA/α-CD represented exclusion complex in which aminobenzoic moiety aromatic pteridine ring remain outside cyclodextrin cavity, while glutamate residue is anchored interior α-cyclodextrin. A...
The CABS coarse-grained model is a well-established tool for modeling globular proteins (predicting their structure, dynamics, and interactions). Here we introduce an extension of the representation force field (CABS-membrane) to effect biological membrane environment on structure proteins. We validate CABS-membrane in folding simulations 10 short helical not using any knowledge about structure. start from random protein conformations placed outside allow full flexibility modeled during...
Effects of benzo[a]pyrene (BaP) on the surface properties dipalmitoyl phosphatidylcholine (DPPC) being basic component pulmonary surfactant and lipid membranes were studied experimentally analyzed by molecular dynamics simulations. Isotherms compressibility mixed BaP/DPPC monolayers water determined using Langmuir-Wilhelmy film balance. It was demonstrated that BaP induced concentration-dependent deviations from initial activity phospholipid a noticeable decrease its fluidity. Results...
Novel conjugates (CP) of moxifloxacin (MXF) with fatty acids (1m-16m) were synthesized good yields utilizing amides chemistry. They exhibit a more pronounced cytotoxic potential than the parent drug. most effective for prostate cancer cells an IC50 below 5 µM respective sorbic (2m), oleic (4m), 6-heptenoic (10m), linoleic (11m), caprylic (15m), and stearic (16m) acids. All derivatives evaluated against panel standard clinical bacterial strains, as well towards mycobacteria. The highest...
Sixteen new Ciprofloxacin derivatives were designed and successfully synthesized. In an in silico experiment, lipophilicity was established for obtained compounds. All compounds screened antimicrobial activity using standard clinical strains. As Gram-positive hospital microorganisms, all tested active. Measured MICs the range 1–16 µg/mL, confirming high potency. Derivative 12 demonstrated against Staphylococci, within of 0.8–1.6 µg/mL confirmed as leading structure with 1 S. pasteuri KR 4358...
The presence of disulfide bonds affects the protein stability and therefore tendency to misfold form amyloid-like fibrils. Insulin's three bridges stabilize native state prevent aggregation. Partial proteolysis insulin releases highly amyloidogenic inherently disordered two-chain 'H-fragment' retaining insulin's Cys7A-Cys7B Cys6A-Cys11A bonds. abrupt self-association H-fragment monomers into fibrils is suppressed in disulfide-reducing agent. These circumstances make an interesting model...
The CABS model can be applied to a wide range of protein-protein and protein-peptide molecular modeling tasks, such as simulating folding pathways, predicting structures, docking, analyzing the structural dynamics complexes. In this work, we use CABS-dock tool in two diverse tasks: 1) structures amyloid protofilaments 2) identifying cleavage sites peptide substrates proteolytic enzymes. first case, simulations simultaneous docking amyloidogenic peptides indicated that accurately predict...