A5051123981- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- Advanced biosensing and bioanalysis techniques
- Protein Structure and Dynamics
- Science and Education Research
- RNA Interference and Gene Delivery
- Nanoparticle-Based Drug Delivery
- Glycosylation and Glycoproteins Research
- Graphene and Nanomaterials Applications
- HIV Research and Treatment
- Carbohydrate Chemistry and Synthesis
- Bacterial Genetics and Biotechnology
- Phonetics and Phonology Research
- Scientific Computing and Data Management
- Molecular Junctions and Nanostructures
- HIV/AIDS drug development and treatment
- Surface Chemistry and Catalysis
- Distributed and Parallel Computing Systems
- Research Data Management Practices
- Electrospun Nanofibers in Biomedical Applications
- Education and Digital Technologies
- Plant biochemistry and biosynthesis
- Rural and Ethnic Education
- Plant nutrient uptake and metabolism
- Cloud Computing and Resource Management
University of California, Riverside
2020-2024
Universidade Federal de São Carlos
2023
Universidade Federal do Rio Grande do Sul
2012-2021
Universidade Federal de Ciências da Saúde de Porto Alegre
2019-2021
CRISPR-Cas9 (clustered regularly interspaced short palindromic repeat and associated Cas9 protein) is a molecular tool with transformative genome editing capabilities. At the level, an intricate allosteric signaling critical for DNA cleavage, but its role in specificity enhancement of endonuclease poorly understood. Here, multi-microsecond dynamics combined solution NMR graph theory-derived models to probe key specificity-enhancing mutations. We show that mutations responsible increasing...
Abstract CRISPR-based DNA adenine base editors (ABEs) hold remarkable promises to address human genetic diseases caused by point mutations. ABEs were developed combining CRISPR-Cas9 with a transfer RNA (tRNA) adenosine deaminase enzyme and through directed evolution, conferring the ability deaminate DNA. However, molecular mechanisms driving efficient deamination in evolved remain unresolved. Here, extensive simulations biochemical experiments reveal biophysical basis behind astonishing...
Ipecac alkaloids are secondary metabolites produced in the medicinal plant Psychotria ipecacuanha. Emetine is main alkaloid of ipecac and one active compounds syrup with emetic property. Here we evaluated emetine’s potential as an antiviral agent against Human Immunodeficiency Virus. We performed vitro Reverse Transcriptase (RT) Assay Natural Endogenous Activity (NERT) to evaluate HIV RT inhibition. molecular docking on HIV-1 was also analyzed. Phenotypic assays were non-lymphocytic...
ADVERTISEMENT RETURN TO ISSUEPREVFirst ReactionsNEXTFighting COVID-19 Using Molecular Dynamics SimulationsMolecular dynamics simulations revealed a promising immune target on the SARS-CoV-2 spike protein, proposing novel strategies for vaccine development.Pablo R. ArantesPablo ArantesDepartment of Bioengineering, University California Riverside, 900 Avenue, 92512, United StatesMore by Pablo Arantes, Aakash SahaAakash SahaDepartment Sahahttp://orcid.org/0000-0003-0776-9771, and Giulia...
Recent empirical studies have highlighted the large degree of analytic flexibility in data analysis that can lead to substantially different conclusions based on same set. Thus, researchers expressed their concerns these researcher degrees freedom might facilitate bias and claims do not stand test time. Even greater is be expected fields which primary lend themselves a variety possible operationalizations. The multidimensional, temporally extended nature speech constitutes an ideal testing...
CRISPR-Cas12a is a genome-editing system, recently also harnessed for nucleic acid detection, which promising the diagnosis of SARS-CoV-2 coronavirus through DETECTR technology. Here, collective ensemble multimicrosecond molecular dynamics characterizes key dynamic determinants allowing processing in CRISPR-Cas12a. We show that DNA binding induces switch conformational Cas12a, results activation peripheral REC2 and Nuc domains to enable cleavage acids. The simulations reveal large-amplitude...
Abstract Allostery is a fundamental property of proteins, which regulates biochemical information transfer between spatially distant sites. Here, we report on the critical role molecular dynamics (MD) simulations in discovering mechanism allosteric communication within CRISPR‐Cas9, leading genome editing machinery with enormous promises for medicine and biotechnology. MD revealed how allostery intervenes during at least three steps CRISPR‐Cas9 function: affecting DNA recognition, mediating...
Many bacteria possess type-II immunity against invading phages or plasmids known as the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated 9 (Cas9) system to detect and degrade foreign DNA sequences. The Cas9 protein has two endonucleases responsible for double-strand breaks (the HNH domain cleaving target strand of duplexes RuvC nontarget strand, respectively) a single-guide RNA-binding where RNA strands are base-paired. Three engineered single Lys-to-Ala...
Metadynamics calculations of large chemical systems with ab initio methods are computationally prohibitive due to the extensive sampling required simulate degrees freedom in these systems. To address this computational bottleneck, we utilized a GPU-enhanced density functional tight binding (DFTB) approach on massively parallelized cloud computing platform efficiently calculate thermodynamics and metadynamics biochemical first validate our approach, calculated free-energy surfaces alanine...
Deep learning approaches like AlphaFold 2 (AF2) have revolutionized structural biology by accurately predicting the ground state structures of proteins. Recently, clustering and subsampling techniques that manipulate multiple sequence alignment (MSA) inputs into to generate conformational ensembles proteins also been proposed. Although many these made open source, they often require integrating packages can be challenging for researchers who a limited programming background employ. This is...
The Vibrio cholerae Cascade–TniQ complex unveiled a new paradigm in biology, demonstrating that CRISPR-associated proteins can direct DNA transposition. Despite the tremendous potential of “knocking-in” genes at desired sites, mechanisms underlying binding and transposition remain elusive. In this system, conformational change Cas8 protein is essential for binding, yet how it occurs unclear. Here, structural modeling free energy simulations reconstruct helical bundle reveal an open–closed...
The pressing need for clinical diagnostics has required the development of novel nucleic acid-based detection technologies that are sensitive, fast, and inexpensive, can be deployed at point-of-care. Recently, RNA-guided ribonuclease CRISPR-Cas13 been successfully harnessed such purposes. However, developing assays genetic variability, example single-nucleotide polymorphisms, is still challenging previously described design strategies not always generalizable. Here, we expanded our...
The last step of the bacterial N-glycosylation pathway involves PglB, an oligosaccharyltransferase, which is responsible for en bloc transfer a fully assembled oligosaccharide chain to protein possessing extended motif D/E-X-N-X-S/T. Recently, this molecule had its full structure elucidated, enabling description domains and proposition catalytic mechanism. By employing molecular dynamics simulations, we were able evaluate structural aspects suggesting prevalent motions that may bring...
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Chalcones and flavonoids constitute a large family of plant secondary metabolites that have been explored as potential source novel pharmaceutical products. While the simulation these compounds by molecular dynamics (MD) can be valuable strategy to assess their conformational properties so further develop role in drug discovery, there are no set force field parameters specifically designed experimentally validated for description condensed phase. So current work developed new parameter MD...