A5031922601- Receptor Mechanisms and Signaling
- Computational Drug Discovery Methods
- Chemical Synthesis and Analysis
- Neuropeptides and Animal Physiology
- Bioinformatics and Genomic Networks
- Monoclonal and Polyclonal Antibodies Research
- Microbial Natural Products and Biosynthesis
- Protein Structure and Dynamics
- Mast cells and histamine
- Diabetes Treatment and Management
- Machine Learning in Materials Science
- Phosphodiesterase function and regulation
- Synthesis and Catalytic Reactions
- Analytical Chemistry and Chromatography
- Trypanosoma species research and implications
- Machine Learning in Bioinformatics
- Microtubule and mitosis dynamics
- Genetics, Bioinformatics, and Biomedical Research
- Synthesis and Biological Evaluation
- Nicotinic Acetylcholine Receptors Study
- 14-3-3 protein interactions
- Chemical synthesis and alkaloids
- Cell Image Analysis Techniques
- Scientific Computing and Data Management
- Melanoma and MAPK Pathways
University of Copenhagen
2018-2024
Vrije Universiteit Amsterdam
2012-2024
Heptares Therapeutics (United Kingdom)
2021
Science for Life Laboratory
2021
Uppsala University
2021
Radboud University Medical Center
2016-2018
Amsterdam UMC Location Vrije Universiteit Amsterdam
2014-2018
Radboud University Nijmegen
2016-2018
Radboud Institute for Molecular Life Sciences
2017-2018
University Medical Center
2016
G protein-coupled receptors (GPCRs) form both the largest family of membrane proteins and drug targets, mediating action one-third medicines. The GPCR database, GPCRdb serves >4 000 researchers every month offers reference data, analysis own or literature experiment design dissemination published datasets. Here, we describe new updated resources with a particular focus on integration sequence, structure function. contains all human non-olfactory GPCRs (and >27 orthologs), G-proteins...
Protein kinases regulate the majority of signal transduction pathways in cells and have become important targets for development designer drugs. We present a systematic analysis kinase-ligand interactions all regions catalytic cleft 1252 human cocrystal structures Data Bank (PDB). The interaction fingerprints structure database (KLIFS) contains consistent alignment 85 kinase ligand binding site residues that enables identification family specific features classification ligands according to...
Abstract Two-thirds of human hormones and one-third clinical drugs activate ~350 G-protein-coupled receptors (GPCR) belonging to four classes: A, B1, C F. Whereas a model activation has been described for class very little is known about the other classes, which differ by being activated endogenous ligands bound mainly or entirely extracellularly. Here we show that, although they use same structural scaffold share several ‘helix macroswitches’, GPCR classes in their ‘residue microswitch’...
G protein-coupled receptors (GPCRs) are physiologically abundant signaling hubs routing hundreds of extracellular signal substances and drugs into intracellular pathways. The GPCR database, GPCRdb supports >5000 interdisciplinary researchers every month with reference data, analysis, visualization, experiment design dissemination. Here, we present our fifth major release setting out an overview the many resources for receptor sequences, structures, ligands. This includes recently published...
The recent crystal structure determinations of druggable class A G protein-coupled receptors (GPCRs) have opened up excellent opportunities in structure-based ligand discovery for this pharmaceutically important protein family. We developed and validated a customized virtual fragment screening protocol against the recently determined human histamine H(1) receptor (H(1)R) structure. method combines molecular docking simulations with protein-ligand interaction fingerprint (IFP) scoring method....
Protein kinases play a crucial role in cell signaling and are important drug targets several therapeutic areas. The KLIFS database contains detailed structural kinase-ligand interaction information derived from all (>2900) structures of catalytic domains human mouse protein deposited the Data Bank order to provide insights into determinants binding selectivity. kinase have been processed consistent manner by systematically analyzing features molecular fingerprints (IFPs) predefined set 85...
Abstract Kinases are a prime target of drug development efforts with >60 approvals in the past two decades. Due to research into this protein family, wealth data has been accumulated that keeps on growing. KLIFS—Kinase–Ligand Interaction Fingerprints and Structures—is structural database focusing how kinase inhibitors interact their targets. The aim KLIFS is support (structure-based) through systematic collection, annotation, processing structures. Now, 5 years after releasing initial...
Abstract The ability of scoring functions to correctly select and rank docking poses small molecules in protein binding sites is highly target dependent, which presents a challenge for structure-based drug discovery. Here we describe virtual screening method that combines an energy-based function with molecular interaction fingerprint (IFP) identify new ligands based on G protein-coupled receptor (GPCR) crystal structures. consensus prospectively evaluated by: 1) the discovery chemically...
Abstract Despite decades of intensive search for compounds that modulate the activity particular protein targets, a large proportion human kinome remains as yet undrugged. Effective approaches are therefore required to map massive space unexplored compound–kinase interactions novel and potent activities. Here, we carry out crowdsourced benchmarking predictive algorithms kinase inhibitor potencies across multiple families tested on unpublished bioactivity data. We find top-performing...
Abstract Two-thirds of signaling substances, several sensory stimuli and over one-third drugs act via receptors coupling to G proteins. Here, we present an online platform for protein research with reference data tools analysis, visualization design scientific studies across disciplines areas. This may help translate new pharmacological, structural genomic into insights on vital human physiology medicine. The database is accessible at https://gproteindb.org.
Abstract G protein-coupled receptors (GPCRs) are membrane-spanning transducers mediating the actions of numerous physiological ligands and drugs. The GPCR database GPCRdb supports a large global research community with reference data, analysis, visualization, experiment design dissemination. Here, we describe our sixth major release starting an overview all resources for ligands. As addition, ∼400 human odorant their orthologs in model organisms can now be studied across various data tool...
Objective A prospective, randomized, double-blind, placebo-controlled multicenter trial was undertaken in 205 patients treated with total gastrectomy for gastric malignancies to evaluate whether local antimicrobial measures reduce the incidence of esophagojejunal anastomotic leakage. Summary Background Data Anastomotic leakage esophagojejunostomy is always a septic complication malignancies, but it never has been attempted prevent this administration topical agents during critical phase...
Background and Purpose Chemogenomics focuses on the discovery of new connections between chemical biological space leading to protein targets biologically active molecules. G ‐protein coupled receptors ( GPCRs ) are a particularly interesting family for chemogenomics studies because there is an overwhelming amount ligand binding affinity data available. The increasing number aminergic GPCR crystal structures now first time allows integration with high‐resolution structural analyses ‐ligand...
Abstract The number of structures and molecular dynamics simulations proteins is exploding owing to dramatic advances in cryo-electron microscopy, crystallography, computing. One the most powerful ways analyze structural information involves comparisons interatomic interactions across different or same protein related from family ( e.g. GPCRs). Such comparative analyses are interest a wide range researchers but currently prove challenging for all few. To facilitate analyses, we have...
Virtual fragment screening (VFS) is a promising new method that uses computer models to identify small, fragment-like biologically active molecules as useful starting points for fragment-based drug discovery (FBDD). Training sets of true and inactive construct validate target customized VFS methods are however lacking. We have the first time explored possibilities challenges using molecular fingerprints derived from unique set affinity data histamine H(3) receptor (H(3)R), pharmaceutically...
A systematic analysis is presented of the 220 phosphodiesterase (PDE) catalytic domain crystal structures present in Protein Data Bank (PDB) with a focus on PDE–ligand interactions. The consistent structural alignment 57 PDE ligand binding site residues enables interaction fingerprints (IFPs), identification subtype-specific features, and classification ligands according to their modes. We illustrate how mining this structure annotated (PDEStrIAn) database provides new insights into...
Noninvasive methods to modulate G protein-coupled receptors (GPCRs) with temporal and spatial precision are in great demand. Photopharmacology uses photons control situ the biological properties of photoswitchable small-molecule ligands, which bodes well for chemical approaches. Integrating light-switchable configurational an azobenzene into ligand core, we developed a bidirectional antagonist toolbox archetypical family A GPCR, histamine H3 receptor (H3R). From 16 newly synthesized...