A5055598973- Genomics and Chromatin Dynamics
- Protein Structure and Dynamics
- Enzyme Structure and Function
- Chromosomal and Genetic Variations
- Genomics and Phylogenetic Studies
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- Bacteriophages and microbial interactions
- SARS-CoV-2 and COVID-19 Research
- Mosquito-borne diseases and control
- Hemoglobin structure and function
- Biofuel production and bioconversion
- Morphological variations and asymmetry
- Erythrocyte Function and Pathophysiology
- DNA and Nucleic Acid Chemistry
- vaccines and immunoinformatics approaches
- Microtubule and mitosis dynamics
- Monoclonal and Polyclonal Antibodies Research
- Bacterial Genetics and Biotechnology
- Protein purification and stability
- Machine Learning in Materials Science
- Enzyme Production and Characterization
- Insect symbiosis and bacterial influences
- Immunotherapy and Immune Responses
Center for Theoretical Biological Physics
2018-2025
Rice University
2019-2025
Universidade Estadual Paulista (Unesp)
2013-2022
Brazilian Center for Research in Energy and Materials
2017-2021
Exact Sciences (United States)
2021
Rutgers, The State University of New Jersey
2021
Rutgers New Jersey Medical School
2021
Bioscience Research
2018
We investigated genome folding across the eukaryotic tree of life. find two types three-dimensional (3D) architectures at chromosome scale. Each type appears and disappears repeatedly during evolution. The architecture that an organism exhibits correlates with absence condensin II subunits. Moreover, depletion converts human to a state resembling seen in organisms such as fungi or mosquitoes. In this state, centromeres cluster together nucleoli, heterochromatin domains merge. propose...
Significance The COVID-19 pandemic has had an unprecedented impact. Although several vaccines have received emergency use authorization, demand created enormous logistical challenges—including supply, access, and distribution—that justify research for alternative strategies. Phage are viruses that only infect bacteria can be safely administered to humans. Here, as a proof-of-concept study, we demonstrate aerosol vaccination with lung-targeted phage particles displaying short SARS-CoV-2 S...
Abstract The link between genomic structure and biological function is yet to be consolidated, it is, however, clear that physical manipulation of the genome, driven by activity a variety proteins, crucial step. To understand consequences forces underlying genome organization, we build coarse-grained polymer model featuring three fundamentally distinct classes interactions: lengthwise compaction, i.e., compaction chromosomes along its contour, self-adhesion among epigenetically similar...
Analyses of ancient DNA typically involve sequencing the surviving short oligonucleotides and aligning to genome assemblies from related, modern species. Here, we report that skin a female woolly mammoth (†Mammuthus primigenius) died 52,000 years ago retained its architecture. We use PaleoHi-C map chromatin contacts assemble genome, yielding 28 chromosome-length scaffolds. Chromosome territories, compartments, loops, Barr bodies, inactive X chromosome (Xi) superdomains persist. The active...
Using computer simulations, we generate cell-specific 3D chromosomal structures and compare them to recently published chromatin obtained through microscopy. We demonstrate using machine learning polymer physics simulations that epigenetic information can be used predict the structural ensembles of multiple human cell lines. Theory predicts chromosome are fluid only described by an ensemble, which is consistent with observation chromosomes exhibit no unique fold. Nevertheless, our analysis...
We use data-driven physical simulations to study the three-dimensional architecture of Aedes aegypti genome. Hi-C maps exhibit both a broad diagonal and compartmentalization with telomeres centromeres clustering together. Physical modeling reveals that these observations correspond an ensemble 3D chromosomal structures are folded over partially condensed. Clustering near nuclear lamina appears be necessary condition for formation observed structures. Further analysis mechanical properties...
High-resolution techniques capable of manipulating from single molecules to millions cells are combined with three-dimensional modeling followed by simulation comprehend the specific aspects chromosomes. From theoretical perspective, energy landscape theory protein folding inspired development minimal chromatin model (MiChroM). In this work, two biologically relevant MiChroM terms were minimized under different conditions, revealing a competition between loci compartmentalization and...
During mitosis, there are significant structural changes in chromosomes. We used a maximum entropy approach to invert experimental Hi-C data generate effective energy landscapes for chromosomal structures at different stages during the cell cycle. Modeled mitotic show hierarchical organization of helices helices. High-periodicity loops span hundreds kilobases or less, while other low-periodicity ones larger genomic separation, spanning several megabases. The ensembles reveal progressive...
Abstract We introduce the Nucleome Data Bank (NDB), a web-based platform to simulate and analyze three-dimensional (3D) organization of genomes. The NDB enables physics-based simulation chromosomal structural dynamics through MEGABASE + MiChroM computational pipeline. input pipeline consists epigenetic information sourced from Encode database; output trajectories motions that accurately predict Hi-C fluorescence insitu hybridization data, as well multiple observations in vivo. As an...
The energy landscape theory has been an invaluable theoretical framework in the understanding of biological processes such as protein folding, oligomerization, and functional transitions. According to theory, folding is funneled toward native state, a conformational state that consistent with principle minimal frustration. It accepted real proteins are selected through natural evolution, satisfying minimum frustration criterion. However, there evidence low degree accelerates folding. We...
The TKSAMC is a web server which calculates protein charge-charge interactions via the Tanford-Kirkwood Surface Accessibility model with Monte Carlo method for sampling different protonation states. optimization of directed mutations has successfully enhanced thermal stability proteins and could be key to engineering improvement. presents electrostatic free energy contribution each polar-charged residue native state stability. Specific residues are suggested mutated improving choice based on...
Applying simulations with structure-based
The folding process of the N-terminal domain ribosomal protein L9 (NTL9) was investigated at constant-pH computer simulations. Evaluation role electrostatic interaction during carried out by including a Debye-Hückel potential into Cα structure-based model (SBM). In this study, charges ionizable residues and are susceptible to solution conditions, such as pH ionic strength, well presence charged groups. Simulations were performed under different pHs, results validated comparing them with...
The accurate and reliable prediction of the 3D structures proteins their assemblies remains difficult even though number solved soars techniques improve. In this study, a free open access web server, AWSEM-Suite, whose goal is to predict monomeric protein tertiary from sequence described. model underlying server's predictions coarse-grained force field which has its roots in neural network ideas that been optimized using energy landscape theory. Employing physically motivated potentials...
Mosquito-borne diseases have become a significant health issue in many regions around the world. For tropical countries, such as Dengue, Zika, and Chikungunya, became epidemic last decades. Health surveillance reports during this period were crucial providing scientific-based information to guide decision making resources allocation control outbreaks. In work, we perform data analysis of Chikungunya epidemics city Rio de Janeiro by applying compartmental mathematical model. Sensitivity...
The human genome is organized within a nucleus where chromosomes fold into an ensemble of different conformations. Chromosome conformation capture techniques such as Hi-C provide information about the architecture by creating 2D heat map. Initially, map experiments were performed in interphase cell lines. Recently, efforts expanded to several organisms, lines, tissues, and cycle phases obtaining high-quality maps challenging. Poor sampled present high sparse matrices compartments located far...
The rational improvement of the enzyme catalytic activity is one most significant challenges in biotechnology. Most conventional strategies used to engineer enzymes involve selecting mutations increase their thermostability. Determining good criteria for choosing these substitutions continues be a challenge. In this work, we combine bioinformatics, electrostatic analysis, and molecular dynamics predict beneficial that may improve thermostability XynA from Bacillus subtilis. First,...
Evaluation of immunogenic epitopes for universal vaccine development in the face ongoing SARS-CoV-2 evolution remains a challenge. Herein, we investigate genetic and structural conservation an immunogenically relevant epitope (C662-C671) spike (S) protein across variants to determine its potential utility as broad-spectrum candidate against coronavirus diseases. Comparative sequence analysis, assessment, molecular dynamics simulations C662-C671 were performed. Mathematical tools employed...
The conformational stability of the Cold shock protein A (CspA) from C. pseudotuberculosis (Cp), a nucleic acid binding in function pH and salt concentration was examined by using differential scanning calorimetry CD spectroscopy combination with computational analysis to identify specify amino acids undergoing change. Our approach identified sodiumbinding site CpCspA at 8.0 significant reduction β-sheet content observed which resulted decrease thermal stability. analyses His30 His65 as...