A5089814380- Protein Structure and Dynamics
- Enzyme Structure and Function
- Dialysis and Renal Disease Management
- SARS-CoV-2 and COVID-19 Research
- RNA and protein synthesis mechanisms
- Surface Modification and Superhydrophobicity
- Computational Drug Discovery Methods
- Electrowetting and Microfluidic Technologies
- CAR-T cell therapy research
- Molecular spectroscopy and chirality
- Erythropoietin and Anemia Treatment
- Monoclonal and Polyclonal Antibodies Research
- COVID-19 Clinical Research Studies
- Central Venous Catheters and Hemodialysis
- Chronic Kidney Disease and Diabetes
- Lymphoma Diagnosis and Treatment
- Muscle and Compartmental Disorders
- Estrogen and related hormone effects
- Iron Metabolism and Disorders
- Renal and Vascular Pathologies
- Renal Diseases and Glomerulopathies
- Advanced NMR Techniques and Applications
- Blood Pressure and Hypertension Studies
- Cell Adhesion Molecules Research
- Mosquito-borne diseases and control
Università della Svizzera italiana
2016-2025
SIB Swiss Institute of Bioinformatics
2018-2024
University of Lausanne
2024
Alessandro Manzoni Hospital
2012-2023
Institute of Oncology Research
2015-2018
Italian Institute of Technology
2017
University of Cambridge
2007-2016
University of Twente
2015-2016
University of Illinois Urbana-Champaign
2016
Massachusetts Institute of Technology
2016
NMR spectroscopy plays a major role in the determination of structures and dynamics proteins other biological macromolecules. Chemical shifts are most readily accurately measurable parameters, they reflect with great specificity conformations native nonnative states proteins. We show, using 11 examples representative structural classes containing up to 123 residues, that it is possible use chemical as restraints combination conventional molecular mechanics force field determine at resolution...
Protein-folding intermediates have been implicated in amyloid fibril formation involved neurodegenerative disorders. However, the structural mechanisms by which initiate fibrillar aggregation remained largely elusive. To gain insight, we used relaxation dispersion nuclear magnetic resonance spectroscopy to determine structure of a low-populated, on-pathway folding intermediate A39V/N53P/V55L (A, Ala; V, Val; N, Asn; P, Pro; L, Leu) Fyn SH3 domain. The carboxyl terminus remains disordered...
Researchers present a Bayesian inference method for heterogeneous systems that integrates prior information with noisy experimental data.
Abstract Infection with severe acute respiratory syndrome coronavirus 2 associates diverse symptoms, which can persist for months. While antiviral antibodies are protective, those targeting interferons and other immune factors associated adverse disease 2019 (COVID-19) outcomes. Here we discovered that against specific chemokines were omnipresent post-COVID-19, favorable outcome negatively correlated the development of long COVID at 1 yr post-infection. Chemokine also present in HIV-1...
Emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants diminishes the efficacy vaccines and antiviral monoclonal antibodies. Continued development immunotherapies vaccine immunogens resilient to viral evolution is therefore necessary. Using coldspot-guided antibody discovery, a screening approach that focuses on portions virus spike glycoprotein are both functionally relevant averse change, we identified human neutralizing antibodies highly conserved epitopes....
Accumulating senescent cells within tissues contribute to the progression of aging and age-related diseases. Botanical extracts, rich in phytoconstituents, present a useful resource for discovering therapies that could target senescence thus improve healthspan. Here, we show daily oral administration standardized extract Salvia haenkei (Haenkenium (HK)) extended lifespan healthspan naturally aged mice. HK treatment inhibited age-induced inflammation, fibrosis markers across several tissues,...
The emergence of Omicron lineages and descendent subvariants continues to present a severe threat the effectiveness vaccines therapeutic antibodies. We have previously suggested that an insufficient mucosal immunoglobulin A (IgA) response induced by mRNA is associated with surge in breakthrough infections. Here, we further show intramuscular and/or inactivated cannot sufficiently boost secretory IgA uninfected individuals, particularly against variant. thus engineered characterized...
We present a method, CamShift, for the rapid and accurate prediction of NMR chemical shifts from protein structures. The calculations performed by CamShift are based on an approximate expression in terms polynomial functions interatomic distances. Since these very fast to compute readily differentiable, approach can be utilized standard structure calculation protocols.
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...
In order to characterise the dynamics of proteins, a well-established method is incorporate experimental parameters as replica-averaged structural restraints into molecular simulations. Here, we justify this approach in case interproton distance information provided by nuclear Overhauser effects showing that it generates ensembles conformations according maximum entropy principle. These results indicate use simulations, given force field and set data, can provide an accurate approximation...
The mechanisms by which peptides and proteins form ordered aggregates are not well understood. Here we focus on the physicochemical properties of amino acids that favor aggregation suggest a parameter-free model is able to predict change rates over large set natural sequences. Furthermore, results correlate with propensities designed computer simulations.
Abstract The relative wettability of oil and water on solid surfaces is generally governed by a complex competition molecular interaction forces acting in such three-phase systems. Herein, we experimentally demonstrate how the adsorption nature abundant divalent Ca 2+ cations to solid-liquid interfaces induces macroscopic wetting transition from finite contact angles (≈10°) with near-zero without cations. We developed quantitative model based DLVO theory that this transition, which observed...
We used nuclear magnetic resonance data to determine ensembles of conformations representing the structure and dynamics calmodulin (CaM) in calcium-bound state (Ca2+-CaM) bound myosin light chain kinase (CaM-MLCK). These reveal that Ca2+-CaM includes a range structures similar those present when CaM is MLCK. Detailed analysis demonstrates correlated motions within direct structural fluctuations toward complex-like substates. This phenomenon enables initial ligation MLCK at C-terminal domain...
Following the recognition that NMR chemical shifts can be used for protein structure determination, rapid advances have recently been made in methods extending this strategy proteins and complexes of increasing size complexity. A remaining major challenge is to develop approaches exploit information contained about conformational fluctuations native states proteins. In work we show it possible determine an ensemble conformations representing free energy surface RNase using as...
A statistical mechanics description of complex molecular systems involves the determination ensembles conformations that represent their Boltzmann distributions. The observable properties these can be then predicted by calculating averages over such ensembles. In principle, given accurate energy functions and efficient sampling methods, generated dynamics simulations. practice, however, often are known only approximately carried out in a limited manner. We describe here method enables to...