A5052052896- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- RNA Research and Splicing
- Bacteriophages and microbial interactions
- Virus-based gene therapy research
- Ultrasound and Hyperthermia Applications
- Enzyme Structure and Function
- Protein Structure and Dynamics
- Iron Metabolism and Disorders
- SARS-CoV-2 and COVID-19 Research
- Advanced Electron Microscopy Techniques and Applications
- Spectroscopy and Quantum Chemical Studies
- Nuclear Structure and Function
- Microbial Inactivation Methods
- HVDC Systems and Fault Protection
- Viral gastroenteritis research and epidemiology
- Advanced biosensing and bioanalysis techniques
- Animal Virus Infections Studies
- Hemoglobinopathies and Related Disorders
- Chemical Synthesis and Analysis
- Nanopore and Nanochannel Transport Studies
- Phytoplasmas and Hemiptera pathogens
- Diatoms and Algae Research
- Plant Micronutrient Interactions and Effects
- Cytomegalovirus and herpesvirus research
Stanford University
2020-2025
Applied BioPhysics (United States)
2024
Institute of Bioorganic Chemistry, Polish Academy of Sciences
2023
University of California, San Diego
2018
Harvey Mudd College
2018
Abstract The prediction of RNA three‐dimensional structures remains an unsolved problem. Here, we report assessments structure predictions in CASP15, the first CASP exercise that involved modeling. Forty‐two predictor groups submitted models for at least one twelve RNA‐containing targets. These were evaluated by RNA‐Puzzles organizers and, separately, a CASP‐recruited team using metrics (GDT, lDDT) and approaches ( Z ‐score rankings) initially developed assessment proteins generalized here...
Abstract Prediction categories in the Critical Assessment of Structure (CASP) experiments change with need to address specific problems structure modeling. In CASP15, four new prediction were introduced: RNA structure, ligand‐protein complexes, accuracy oligomeric structures and their interfaces, ensembles alternative conformations. This paper lists technical specifications for these describes integration CASP data management system.
The stability and function of biomolecules are directly influenced by their myriad interactions with water. In this study, we investigated water through cryogenic electron microscopy (cryo-EM) on a highly solvated molecule, the Tetrahymena ribozyme, determined at 2.2 2.3 Å resolutions. By employing segmentation-guided ion modeling (SWIM), an approach combining resolvability chemical parameters, automatically modeled cross-validated molecules Mg 2+ ions in ribozyme core, revealing extensive...
Enzymes exist in ensembles of states that encode the energetics underlying their catalysis. Conformational built from 1231 structures 17 serine proteases revealed atomic-level changes across reaction states. By comparing enzymatic and solution reaction, we identified molecular features provide catalysis quantified energetic contributions to Serine precisely position reactants destabilized conformers, creating a downhill gradient selectively favors motions required for while limiting...
Alchemical free energy (AFE) calculations based on molecular dynamics (MD) simulations are key tools in both improving our understanding of a wide variety biological processes and accelerating the design optimization therapeutics for numerous diseases. Computing power theory have, however, long been insufficient to enable AFE be routinely applied early stage drug discovery. One major difficulties performing is length time required converge an ensemble average. CPU implementations MD-based...
The rapid spread of COVID-19 is motivating development antivirals targeting conserved SARS-CoV-2 molecular machinery. genome includes RNA elements that offer potential small-molecule drug targets, but most their 3D structures have not been experimentally characterized. Here, we provide a compilation chemical mapping data from our and other labs, secondary structure models, model ensembles based on Rosetta's FARFAR2 algorithm for regions including the individual stems SL1-8 in extended 5'...
Abstract The first RNA category of the Critical Assessment Techniques for Structure Prediction competition was only made possible because scientists who provided experimental structures to challenge predictors. In this article, these offer a unique and valuable analysis both successes areas improvement in predicted models. All 10 RNA‐only targets yielded predictions topologically similar experimentally determined structures. For one target, experimentalists were able phase their x‐ray...
Prediction of RNA structure from sequence remains an unsolved problem, and progress has been slowed by a paucity experimental data. Here, we present Ribonanza, dataset chemical mapping measurements on two million diverse sequences collected through Eterna other crowdsourced initiatives. Ribonanza enabled solicitation, training, prospective evaluation deep neural networks Kaggle challenge, followed distillation into single, self-contained model called RibonanzaNet. When fine tuned auxiliary...
Abstract Drug discovery campaigns against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) are beginning to target the viral RNA genome 1, . The frameshift stimulation element (FSE) of SARS-CoV-2 is required for balanced expression essential proteins and highly conserved, making it a potential candidate antiviral targeting by small molecules oligonucleotides 3–6 To aid global efforts focusing on frameshifting, we report exploratory results from frameshifting cellular replication...
Abstract The prediction of RNA three-dimensional structures remains an unsolved problem. Here, we report assessments structure predictions in CASP15, the first CASP exercise that involved modeling. Forty two predictor groups submitted models for at least one twelve RNA-containing targets. These were evaluated by RNA-Puzzles organizers and, separately, a CASP-recruited team using metrics (GDT, lDDT) and approaches (Z-score rankings) initially developed assessment proteins generalized here...
Abstract Enzymes exist in ensembles of states that encode the energetics underlying their catalysis. Conformational built from 1231 structures 17 serine proteases reveal atomic-level changes across reaction states, identify molecular features provide catalysis, and quantify energetic contributions to These enzymes precisely position reactants destabilized conformers, creating a downhill gradient selectively favors motions required for while limiting off-pathway conformational states. A local...
Coronavirus genomes sequester their start codons within stem-loop 5 (SL5), a structured, 5′ genomic RNA element. In most alpha- and betacoronaviruses, the secondary structure of SL5 is predicted to contain four-way junction helical stems, some which are capped with UUYYGU hexaloops. Here, using cryogenic electron microscopy (cryo-EM) computational modeling biochemically determined structures, we present three-dimensional structures from six coronaviruses. The domain betacoronavirus...
RNA-Puzzles is a collective endeavor dedicated to the advancement and improvement of RNA three-dimensional structure prediction. With agreement from structural biologists, structures are predicted by modeling groups before publication experimental structures. We report large-scale set predictions 18 for 23 RNA-Puzzles: 4 elements, 2 Aptamers, Viral 5 Ribozymes 8 Riboswitches. describe automatic assessment protocols comparisons between prediction experiment. Our analyses reveal some critical...
CASP assessments primarily rely on comparing predicted coordinates with experimental reference structures. However, structures by their nature are only models themselves-their construction involves a certain degree of subjectivity in interpreting density maps and translating them to atomic coordinates. Here, we directly utilized evaluate the predictions employing method for ranking quality protein chain based fit into density. The fit-based was found correlate well assessment scores....
Prediction categories in the Critical Assessment of Structure (CASP) experiments change with need to address specific problems structure modeling. In CASP15, four new prediction were introduced: RNA structure, ligand-protein complexes, accuracy oligomeric structures and their interfaces, ensembles alternative conformations. This paper lists technical specifications for these describes integration CASP data management system.
Abstract Myriad families of natural RNAs have been proposed, but not yet experimentally shown, to form biologically important structures. Here we report three-dimensional structures three large ornate bacterial using cryogenic electron microscopy at resolutions 2.9-3.1 Å. Without precedent among previously characterized RNA molecules, Giant, Ornate, Lake- and Lactobacillales-Derived (GOLLD), Rumen-Originating, Large (ROOL), Ornate Extremophilic (OLE) homo-oligomeric complexes whose...
Abstract The serum iron level in humans is tightly controlled by the action of hormone hepcidin on efflux transporter ferroportin. Hepcidin negatively regulates absorption and recycling inducing ferroportin internalization degradation. Aberrant activity can lead to diseases overload, like hemochromatosis, or limitation anemias. Here, we determined cryogenic electron microscopy (cryo-EM) structures lipid nanodiscs, both apo state complex with cobalt, an mimetic, hepcidin. These accompanying...
RNA cryo-EM is a fast advancing field.It has solved structures yet unsolved by x-ray crystallography such as the tetrahymena ribozyme and pushed boundaries of resolving small molecules; down to 28kDa.We are now able propose atomic models RNA, guided maps, ranging from 10Å resolution below 3Å.However, these should not be viewed equal various features in particular backbone, resolved resolution-dependent manner.We have analyzed published unpublished maps systematically address resolvability at...
The first RNA category of the CASP competition was only made possible because scientists who provided experimental structures to challenge predictors.In this article, these offer a unique and valuable analysis both successes areas for improvement in predicted models.All ten RNA-only targets yielded predictions topologically similar experimentally determined structures.For one target, experimentalists were able phase their X-ray diffraction data by molecular replacement, showing potential...
CASP assessments primarily rely on comparing predicted coordinates with experimental reference structures. However, errors in the structures can potentially reduce accuracy of assessment. This issue is particularly prominent cryoEM-determined structures, and therefore, assessment CASP15 cryoEM targets, we directly utilized density maps to evaluate predictions. A method for ranking quality protein chain predictions based rigid fitting was found correlate well scores. Overall, evaluation...