A5035048768- Protein Structure and Dynamics
- Protein Degradation and Inhibitors
- Enzyme Structure and Function
- Computational Drug Discovery Methods
- Peptidase Inhibition and Analysis
- RNA and protein synthesis mechanisms
- Advanced biosensing and bioanalysis techniques
- RNA modifications and cancer
- Redox biology and oxidative stress
- Multiple Myeloma Research and Treatments
- Monoclonal and Polyclonal Antibodies Research
- Cancer, Hypoxia, and Metabolism
- Chemical Synthesis and Analysis
- Alzheimer's disease research and treatments
- Fluorine in Organic Chemistry
- Metabolomics and Mass Spectrometry Studies
- HIV/AIDS drug development and treatment
- Cancer-related gene regulation
- Glutathione Transferases and Polymorphisms
- Chromatin Remodeling and Cancer
- Click Chemistry and Applications
- Spectroscopy and Quantum Chemical Studies
- Axon Guidance and Neuronal Signaling
- Prion Diseases and Protein Misfolding
- Synthesis and biological activity
University of Zurich
2016-2025
Boston University
2024
Swedish University of Agricultural Sciences
2010
University of Chicago
2010
University of Jyväskylä
2010
Institute for Atomic and Molecular Physics
2010
National Heart Lung and Blood Institute
2009
National Institutes of Health
2009
Dulbecco Telethon Institute
2009
University of Modena and Reggio Emilia
2009
Species extinctions pose serious threats to the functioning of ecological communities worldwide. We used two qualitative and quantitative pollination networks simulate extinction patterns following three removal scenarios: random systematic strongest weakest interactors. accounted for pollinator behaviour by including potential links into temporal snapshots (12 consecutive 2-week networks) reflect mutualists' ability 'switch' interaction partners (re-wiring). Qualitative data suggested a...
The chromatin-associated enzyme PARP1 has previously been suggested to ADP-ribosylate histones, but the specific ADP-ribose acceptor sites have remained enigmatic. Here, we show that covalently ADP-ribosylates amino-terminal histone tails of all core histones. Using biochemical tools and novel electron transfer dissociation mass spectrometric protocols, identify for first time K13 H2A, K30 H2B, K27 K37 H3, as well K16 H4 sites. Multiple explicit water molecular dynamics simulations tail...
Abstract The RNA methylase METTL3 catalyzes the transfer of a methyl group from cofactor S‐adenosyl‐L‐methionine (SAM) to N 6 atom adenine. We have screened library 4000 analogues and derivatives adenosine moiety SAM by high‐throughput docking into METTL3. Two series adenine were identified in silico , binding mode six predicted inhibitors was validated protein crystallography. compounds, one for each series, show good ligand efficiency. propose route their further development potent selective
The methylase METTL3 is the writer enzyme of N6 -methyladenosine (m6 A) modification RNA. Using a structure-based drug discovery approach, we identified inhibitor with potency in biochemical assay 280 nM, while its enantiomer 100 times less active. We observed dose-dependent reduction m6 A methylation level mRNA several cell lines treated already after 16 h treatment, which lasted for at least 6 days. Importantly, prolonged incubation (up to days) did not alter levels other RNA modifications...
High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand libraries can access far greater space, provided that the predictive accuracy sufficient useful Through largest and most diverse virtual HTS campaign reported date, comprising 318 individual projects, we demonstrate our AtomNet® convolutional neural network...
Abstract A solvation term based on the solvent accessible surface area (SASA) is combined with CHARMM polar hydrogen force field for efficient simulation of peptides and small proteins in aqueous solution. Only two atomic parameters are used: one negative favoring direct groups other positive taking into account hydrophobic effect apolar groups. To approximate water screening effects intrasolute electrostatic interactions, a distance‐dependent dielectric function used ionic side chains...
Abstract Summary: Wordom is a versatile program for manipulation of molecular dynamics trajectories and efficient analysis simulations. Original tools in include procedure to evaluate significance sampling principal component as well modules clustering multiple conformations evaluation order parameters folding aggregation. The was developed with special emphasis on user-friendliness, effortless addition new handling large sets trajectories. Availability: distributed full source code (in the...
Understanding the early steps of aggregation at atomic detail might be crucial for rational design therapeutics preventing diseases associated with amyloid deposits. In this paper, heptapeptide GNNQQNY, from N-terminal prion-determining domain yeast protein Sup35, was studied by 20 molecular dynamics runs a total simulation time μs. The simulations generate in-register parallel packing GNNQQNY β-strands that is consistent x-ray diffraction and Fourier transform infrared data. statistically...
An efficient method for calculating the free energy of solvation a (macro)molecule embedded in continuum solvent is presented. It based on fully analytical evaluation volume and spatial symmetry that displaced from around solute atom by its neighboring atoms. The two measures displacement are combined empirical equations to approximate atomic (or self) electrostatic accessible surface area. former directly yields effective Born radius, which used generalized (GB) formula calculate...
Abstract Wordom is a versatile, user‐friendly, and efficient program for manipulation analysis of molecular structures dynamics. The following new modules have been added since the publication original paper in 2007: assignment secondary structure, calculation solvent accessible surfaces, elastic network model, motion cross correlations, protein structure network, shortest intra‐molecular inter‐molecular communication paths, kinetic grouping analysis, mincut‐based free energy profiles. In...
The replica exchange molecular dynamics (REMD) approach is applied to four oligomeric peptide systems. At physiologically relevant temperature values REMD samples conformation space and aggregation transitions more efficiently than constant (CTMD). During the process energetic structural properties are essentially same in CTMD. A condensation stage toward disordered aggregates precedes β-sheet formation. Two order parameters, borrowed from anisotropic fluid analysis, used monitor process....
Abstract The reliable identification of β‐aggregating stretches in protein sequences is essential for the development therapeutic agents Alzheimer's and Parkinson's diseases, as well other pathological conditions associated with deposition. Here, a model based on physicochemical properties computational design peptide shown to be able predict aggregation rate over large set natural polypeptide sequences. Furthermore, identifies aggregation‐prone fragments within proteins predicts parallel or...
Rational ligand design is a complex problem that can be divided into three parts: the search for optimal positions and orientations of functional groups in binding site, connection such to form candidate ligands, estimation their constants. Approaches addressing first two parts are described present work. They applied construction peptide ligands site human immunodeficiency virus 1 (HIV-1) proteinase. The primary objective test method by comparison results with MVT-101 structure which...