A5002139604- Pharmacogenetics and Drug Metabolism
- Computational Drug Discovery Methods
- Geology and Paleoclimatology Research
- Analytical Chemistry and Chromatography
- Metal-Catalyzed Oxygenation Mechanisms
- Geological formations and processes
- Cryospheric studies and observations
- Neuroscience and Neuropharmacology Research
- Drug Transport and Resistance Mechanisms
- Chemical Synthesis and Analysis
- Epigenetics and DNA Methylation
- Microbial Metabolic Engineering and Bioproduction
- Protein Structure and Dynamics
- Amino Acid Enzymes and Metabolism
- Receptor Mechanisms and Signaling
- Histone Deacetylase Inhibitors Research
- Pleistocene-Era Hominins and Archaeology
- Antibiotic Resistance in Bacteria
- Cancer-related gene regulation
- Landslides and related hazards
- Free Radicals and Antioxidants
- Molecular Sensors and Ion Detection
- Synthesis and Biological Evaluation
- Methane Hydrates and Related Phenomena
- earthquake and tectonic studies
Novozymes (Denmark)
2017-2024
Norwegian Geological Survey
2000-2023
Posten (Norway)
2021-2023
University of Copenhagen
2011-2020
University of Montana
2015
Emory University
2015
Vrije Universiteit Amsterdam
2009
Instituto di Biofisica
2008
Lund University
2007-2008
University of Gothenburg
2008
To provide a new reconstruction of the deglaciation Fennoscandian Ice Sheet, in form calendar-year time-slices, which are particularly useful for ice sheet modelling, we have compiled and synthesized published geomorphological data eskers, ice-marginal formations, lineations, marginal meltwater channels, striae, ice-dammed lakes, geochronological from radiocarbon, varve, optically-stimulated luminescence, cosmogenic nuclide dating. This is summarized as map Sheet with isochrons marking every...
SMARTCyp is an in silico method that predicts the sites of cytochrome P450-mediated metabolism druglike molecules. The foremost a reactivity model, and as such, it shows preference for predicting are metabolized by P450 3A4 isoform. site directly from 2D structure molecule, without requiring calculation electronic properties or generation 3D structures. This major advantage, because makes very fast. Other advantages experimental data not prerequisite to create can easily be integrated with...
2-Oxoglutarate and iron dependent oxygenases are therapeutic targets for human diseases. Using a representative 2OG oxygenase panel, we compare the inhibitory activities of 5-carboxy-8-hydroxyquinoline (IOX1) 4-carboxy-8-hydroxyquinoline (4C8HQ) with that two other commonly used inhibitors, N-oxalylglycine (NOG) 2,4-pyridinedicarboxylic acid (2,4-PDCA). The results reveal IOX1 has broad spectrum activity, as demonstrated by inhibition transcription factor hydroxylases, representatives all...
Abstract Summary: The SMARTCyp server is the first web application for site of metabolism prediction cytochrome P450-mediated drug metabolism. Availability: freely available use on at www.farma.ku.dk/smartcyp where Java program and source code also download. Contact: smartcyp@farma.ku.dk; lo@farma.ku.dk Supplementary information: data are Bioinformatics online.
The orphan glutamate-like receptor GluRδ2 is predominantly expressed in Purkinje cells of the central nervous system. classification to ionotropic glutamate family based on sequence similarities, because does not form functional homomeric glutamate-gated ion channels transfected cells. Studies −/− knockout mice as well with naturally occurring mutations gene have demonstrated an essential role cerebellar long-term depression, motor learning, coordination, and synaptogenesis. However, lack a...
We have estimated the activation energy for hydrogen abstraction by compound I in cytochrome P450 a diverse set of 24 small organic substrates using state-of-the-art density functional theory (B3LYP). then show that these results can be reproduced computationally less demanding methods, example, mimics with both B3LYP and semiempirical AM1 method (mean absolute error 3-4 kJ/mol) or calculating bond dissociation energy, without relaxation radical (B3LYP) from three-point fit to Morse...
The fluorescent dye thioflavin T (ThT) is commonly used for in situ amyloid fibril detection. In this work, we focused on the spectroscopic properties and chemical stability of ThT aqueous solution as a function pH, temperature, concentration. A reversible hydroxylation process occurs alkaline solutions, which was characterized using combination UV−vis absorption spectroscopy, proton NMR, density functional theory (DFT). On basis these studies, propose structure hydroxylated form. Finally,...
The serotonin transporter (SERT) regulates extracellular levels of (5-hydroxytryptamine, 5HT) in the brain by transporting 5HT into neurons and glial cells. human SERT (hSERT) is primary target for drugs used treatment emotional disorders, including depression. hSERT belongs to solute carrier 6 family that includes a bacterial leucine (LeuT), which high resolution crystal structure has become available. LeuT proved be an excellent model transporters advanced understanding structure-function...
The serotonin transporter (SERT) regulates extracellular levels of the neurotransmitter (5-hydroxytryptamine) in brain by facilitating uptake released 5-hydroxytryptamine into neuronal cells. SERT is target for widely used antidepressant drugs, including imipramine, fluoxetine, and (S)-citalopram, which are competitive inhibitors transport function. Knowledge molecular details binding sites has been limited due to lack structural data on SERT. Here, we present a characterization...
The cytochrome P450 (P450) superfamily plays an important role in the metabolism of drug compounds, and it is therefore highly desirable to have models that can predict whether a compound interacts with specific isoform P450s. In this work, we provide silico for classification CYP1A2 inhibitors noninhibitors. Training test sets consisted approximately 400 7000 respectively. Various machine learning techniques, such as binary quantitative structure activity relationship, support vector (SVM),...
RS-Predictor is a tool for creating pathway-independent, isozyme-specific, site of metabolism (SOM) prediction models using any set known cytochrome P450 (CYP) substrates and metabolites. Until now, the method was only trained validated on CYP 3A4 data, but in present study, we report versatility modeling paradigm by testing regioselectivity nine most important isozymes. Through curation source literature, have assembled 680 distributed among CYPs 1A2, 2A6, 2B6, 2C19, 2C8, 2C9, 2D6, 2E1,...
Cytochromes P450 are the most important class of drug metabolizing enzymes. Prediction metabolism is in development new drugs, to understand and reduce adverse reactions animal testing.SMARTCyp 3.0 an updated version our previous web server for prediction site-of-metabolism Cytochrome P450-mediated metabolism, now Python 3 with increased structural coverage features. The SMARTCyp program a first principle-based method using density functional theory determined activation energies more than...
Abstract A method is developed for the combination of quantum chemical geometry optimizations and crystallographic structure refinement. The implemented by integrating software Turbomole with Crystallography NMR System (CNS), using three small procedures transferring information between two programs. program ( COMQUM‐X) used to study binding inhibitor N ‐methylmesoporphyrin ferrochelatase, we show that behaves properly leads an improvement inhibitor. It allows us directly quantify in energy...
The oxidation and dealkylation of dimethylsulfoxide (DMSO), dimethylsulfide (DMS), trimethylamine (TMA) by cytochrome P450 has been studied with density functional theory calculations. results show that the reactions always occur on doublet spin surface, whereas dealkylations can take place for both quartet states. Moreover, DMS is more reactive than DMSO, S-oxidation favorable S-dealkylation, N-dealkylation N-oxidation. This in perfect agreement experimental results, showing activation...
With the availability of an increasing number high resolution 3D structures human cytochrome P450 enzymes, structure-based modeling tools are more readily used. In this study we explore possibilities using docking and scoring experiments on 1A2. Three different questions have been addressed: 1. Binding orientations conformations were successfully predicted for various substrates. 2. A virtual screen was performed with satisfying enrichment rates. 3. classification individual compounds into...
Dynamic methylations and demethylations of histone lysine residues are important for gene regulation facilitated by methyltransferases demethylases (HDMs). KDM5B/Jarid1B/PLU1 is an H3K4me3/me2-specific demethylase belonging to the JmjC domain-containing family (JHDMs). Several studies have linked KDM5B breast, prostate skin cancer, highlighting its potential as a drug target. However, most inhibitor focused on other JHDMs, inhibitors remain be explored. Here, we report expression,...
Abstract Cytochrome P450 17A1 (CYP17A1) is an important target in the treatment of prostate cancer because it produces androgens required for tumour growth. The FDA has approved only one CYP17A1 inhibitor, abiraterone, which contains a steroidal scaffold similar to endogenous substrates. Abiraterone structurally substrates other cytochrome enzymes involved steroidogenesis, and interference can pose liability terms side effects. Using non-steroidal scaffolds expected enable design compounds...
Iron porphyrin complexes are cofactors in many important proteins such as cytochromes P450, hemoglobin, heme peroxidases, etc. Many computational studies on these systems have been done over the past decade. In this study, performance of some most commonly used density functional theory functionals is evaluated with regard to how they reproduce experimental structures. Seven different (BP86, PBE, PBE0, TPSS, TPSSH, B3LYP, and B97-D) study eight iron complexes. The results show that TPSS give...