A5077024945- Receptor Mechanisms and Signaling
- Computational Drug Discovery Methods
- Neuropeptides and Animal Physiology
- Protein Structure and Dynamics
- Mass Spectrometry Techniques and Applications
- Lipid Membrane Structure and Behavior
- Monoclonal and Polyclonal Antibodies Research
- Enzyme Structure and Function
- Diabetes Treatment and Management
- Chemical Synthesis and Analysis
- RNA and protein synthesis mechanisms
- Advanced Proteomics Techniques and Applications
- vaccines and immunoinformatics approaches
- Microbial Metabolic Engineering and Bioproduction
- Complement system in diseases
- Cancer, Stress, Anesthesia, and Immune Response
- Adenosine and Purinergic Signaling
- Machine Learning in Bioinformatics
- Cholesterol and Lipid Metabolism
- Protein purification and stability
- Neuroscience and Neuropharmacology Research
- Artificial Intelligence in Healthcare
- ATP Synthase and ATPases Research
- RNA Research and Splicing
- Statistical and Computational Modeling
University of Warsaw
2016-2025
International Institute of Molecular and Cell Biology
2011-2013
European Molecular Biology Organization
2012
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...
The years 2000 and 2007 witnessed milestones in current understanding of G protein-coupled receptor (GPCR) structural biology. In the first GPCR, bovine rhodopsin, was crystallized structure solved, while β(2)-adrenergic receptor, GPCR with diffusible ligands, determined owing to advances microcrystallization an insertion fast-folding lysozyme into receptor. parallel those crystallographic studies, biological biochemical characterization GPCRs has advanced considerably because receptors are...
G protein-coupled receptors (GPCRs) constitute the largest and most frequently used family of molecular drug targets. The simplicity GPCR design results from their common seven-transmembrane-helix topology well-understood signaling pathways. GPCRs are extremely sensitive to slight changes in chemical structure compounds, which allows for reliable highly selective specific drugs. Only recently has number structures, both active inactive conformations, together with ligands, become sufficient...
G-protein coupled receptors (GPCRs) are targets of nearly one third the drugs at current pharmaceutical market. Despite their importance in many cellular processes crystal structures available for less than 20 unique GPCRs Rhodopsin-like class. Fortunately, even though involved different signaling cascades, this large group membrane proteins has preserved a uniform structure comprising seven transmembrane helices that allows quite reliable comparative modeling. Nevertheless, low sequence...
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...
Chemokines modulate the immune response by regulating migration of cells. They are also known to participate in such processes as cell-cell adhesion, allograft rejection, and angiogenesis. interact with two different subfamilies G protein-coupled receptors: conventional chemokine receptors atypical receptors. Here, we focused on former one which has been linked many inflammatory diseases, including: multiple sclerosis, asthma, nephritis, rheumatoid arthritis. Available crystal cryo-EM...
Sphingosine 1-phosphate (S1P) is a lysophospholipid mediator which activates G protein–coupled sphingosine receptors and thus evokes variety of cell tissue responses including lymphocyte trafficking, endothelial development, integrity, maturation. We performed five all-atom 700 ns molecular dynamics simulations the receptor 1 (S1P1) based on recently released crystal structure that with an antagonist. found initial movements amino acid residues occurred in area highly conserved W2696.48 TM6...
A disturbance of glucose homeostasis leading to type 2 diabetes mellitus (T2DM) is one the severe side effects that may occur during a prolonged use many drugs currently available on market. In this manuscript we describe most common cases drug-induced T2DM, discuss pharmacotherapies and propose new ones. Among various incretin therapies have recently focused attention due newly determined crystal structure hormone receptor GLP1R. Incretin receptors: GLP1R GIPR together with glucagon GCGR...
A key component to success in structure-based drug design is reliable information on protein–ligand interactions. Recent development NMR techniques has accelerated this process by overcoming some of the limitations X-ray crystallography and computational docking. In work we present a new scoring protocol based NMR-derived interligand INPHARMA NOEs guide selection computationally generated docking modes. We demonstrate performance range scenarios, encompassing traditionally difficult cases...
Bacteriophages effectively counteract diverse bacterial infections, and their ability to treat most types of cancer has been explored using phage engineering or phage-virus hybrid platforms. In the present study, it was demonstrated that bacteriophage MS2 can affect expression genes associated with proliferation survival LNCaP prostate epithelial cells. cells were exposed at a concentration 1×107 plaque forming units/ml for 24-48 h. After exposure, various cellular parameters, including cell...
The Formyl Peptide Receptor 1 (FPR1) is an important chemotaxis receptor involved in various aspects of host defense and inflammatory processes. We constructed a model FPR1 using as novel template the chemokine CXCR4 from same branch phylogenetic tree G-protein-coupled receptors. previously employed rhodopsin contained bulge at extracellular part TM2 which directly influenced binding ligands. also conducted molecular dynamics (MD) simulations apo form well complexed with agonist fMLF...
Abstract Routine structure prediction of new folds is still a challenging task for computational biology. The challenge not only in the proper determination overall fold but also building models acceptable resolution, useful modeling drug interactions and protein–protein complexes. In this work we propose test comprehensive approach to protein supported by sparse, relatively easy obtain, experimental data. We focus on chemical shift‐based restraints from NMR, although other sparse could be...
Vacuolar ATPases are a potential therapeutic target because of their involvement in variety severe diseases such as osteoporosis or cancer. Archazolide A (1) and related analogs have been previously identified selective inhibitors V-ATPases with potency down to the subnanomolar range. Herein we report on determination ligand binding mode by combination molecular docking, dynamics simulations, biochemical experiments, resulting sound model for inhibitory mechanism this class putative...
The prolonged use of many currently available drugs results in the severe side effect disruption glucose metabolism leading to type 2 diabetes mellitus (T2DM. Gut hormone receptors including glucagon receptor (GCGR) and incretin receptors: glucagon-like peptide 1 (GLP1R) gastric inhibitory polypeptide (GIPR) are important drug targets for treatment T2DM, as they play roles regulation insulin levels food intake. In this study, we hypothesized that could compensate negative influences specific...
The recent GPCR Dock 2013 assessment of serotonin receptor 5-HT1B and 5-HT2B, smoothened SMO targets, exposed the strengths weaknesses currently used computational approaches. test cases 5-HT2B demonstrated that both structure ligand binding mode can be predicted with atomic-detail accuracy, as long target-template sequence similarity is relatively high. On other hand, observation a low similarity, e.g., between from frizzled family members rhodopsin family, hampers prediction docking....
Abstract Recent development of nuclear magnetic resonance (NMR) techniques provided new types structural restraints that can be successfully used in fast and low‐cost global protein fold determination. Here, we present CABS‐NMR, an efficient modeling tool, which takes advantage such restraints. The are converted from original NMR data to fit the coarse grained representation C‐Alpha‐Beta‐Side‐group (CABS) algorithm. CABS is a Monte Carlo search algorithm uses knowledge‐based force field. Its...
Vasoactive intestinal peptide receptor 1 (VPAC1) is a member of secretin-like subfamily G protein-coupled receptors. Its endogenous neuropeptide (VIP), secreted by neurons and immune cells, modulates various physiological functions such as exocrine endocrine secretions, response, smooth muscles relaxation, vasodilation, fetal development. As drug target, VPAC1 has been selected for therapy inflammatory diseases but discovery still hampered lack its crystal structure. In this study we...
The large amount of data that has been collected so far for G protein-coupled receptors requires machine learning (ML) approaches to fully exploit its potential. Our previous ML model based on gradient boosting used prediction drug affinity and selectivity a receptor subtype was compared with explicit information ligand-receptor interactions from induced-fit docking. Both methods have proved their usefulness in response predictions. Yet, successful combination still allosteric/orthosteric...
Several different methods for contact prediction succeeded within the Sixth Critical Assessment of Techniques Protein Structure Prediction (CASP6). The most relevant were non-local predictions targets from difficult categories: fold recognition-analogy and new fold. Such contacts could provide valuable structural information in case a template structure cannot be found PDB.We described comprehensive tests effectiveness data various aspects de novo modeling with CABS, an algorithm which was...
Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) are two neuropeptides that contribute to the regulation of motility secretion, exocrine endocrine secretions, homeostasis immune system. Their biological effects mediated by three receptors named VPAC1, VPAC2 PAC1 belong class B GPCRs. VIP PACAP have been identified as potential therapeutic targets for treatment chronic inflammation, neurodegenerative diseases cancer. However, pharmacological...