23 research outputs found
MODOMICS: a database of RNA modification pathways. 2021 update
No full textThe MODOMICS database has been, since 2006, a manually curated and centralized resource, storing and distributing comprehensive information about modified ribonucleosides. Originally, it only contained data on the chemical structures of modified ribonucleosides, their biosynthetic pathways, the location of modified residues in RNA sequences, and RNA-modifying enzymes. Over the years, prompted by the accumulation of new knowledge and new types of data, it has been updated with new information and functionalities. In this new release, we have created a catalog of RNA modifications linked to human diseases, e.g., due to mutations in genes encoding modification enzymes. MODOMICS has been linked extensively to RCSB Protein Data Bank, and sequences of experimentally determined RNA structures with modified residues have been added. This expansion was accompanied by including nucleotide 5'-monophosphate residues. We redesigned the web interface and upgraded the database backend. In addition, a search engine for chemically similar modified residues has been included that can be queried by SMILES codes or by drawing chemical molecules. Finally, previously available datasets of modified residues, biosynthetic pathways, and RNA-modifying enzymes have been updated. Overall, we provide users with a new, enhanced, and restyled tool for research on RNA modification. MODOMICS is available at https://iimcb.genesilico.pl/modomics/.Issue Section: Database Issue</p
Protein-Mutation-Induced Conformational Changes of the DNA and Nuclease Domain in CRISPR/Cas9 Systems by Molecular Dynamics Simulations
No full textClass 2 CRISPR (clustered
regularly interspaced short palindromic
repeats) systems offer a unique protocol for genome editing in eukaryotic
cells. The nuclease activity of Cas9 has been harnessed to perform
precise genome editing by creating double-strand breaks. However,
the nuclease activity of Cas9 can be triggered when there is imperfect
complementarity between the RNA guide sequence and an off-target genomic
site, which is a major limitation of the CRISPR technique for practical
applications. Hence, understanding the binding mechanisms in CRISPR/Cas9
for predicting ways to increase cleavage specificity is a timely research
target. One way to understand and tune the binding strength is to
study wild-type and mutant Cas9, in complex with a guide RNA and a
target DNA. We have performed classical all-atom MD simulations over
a cumulative time scale of 13.5 μs of CRISPR/Cas9 ternary complexes
with the wild-type Cas9 from Streptococcus pyogenes and three of its mutants: K855A, H982A, and the combination K855A+H982A,
selected from the outcome of experimental work. Our results reveal
significant structural impact of the mutations, with implications
for specificity. We find that the “unwound” part of
the nontarget DNA strand exhibits enhanced flexibility in complexes
with Cas9 mutants and tries to move away from the HNH/RuvC interface,
where it is otherwise stabilized by electrostatic couplings in the
wild-type complex. Our findings refine an electrostatic model by which
cleavage specificity can be optimized through protein mutations
Atomistic Insights into Structural Differences between E3 and E4 Isoforms of Apolipoprotein E
No full textA comparison of four different conformations adopted by human telomeric G‐quadruplex using computer simulations
No full textRadio-bright vs. Radio-dark Gamma-ray Bursts -- More Evidence for Distinct Progenitors
No full textWe analyze two distinct samples of GRBs, with and without radio afterglow
emission. We use a sample of 211 GRBs which is an update of the previous sample
from arXiv:1902.01974, and find, in agreement with previous results (although
with a sample that is almost twice as large) as the intrinsic gamma-ray
duration (Tint) and isotropic equivalent energy (Eiso) distributions between
these two populations appear to differ significantly. The redshift (z)
distributions of the two samples are not statistically different. We analyze
several correlations between variables (Eiso, Tint, jet opening angle, and z),
accounting for selection effects and redshift evolution using the
Efron-Petrosian method. We find a statistically significant anti-correlation
between the jet opening angle and redshift, as well as between Tint and
redshift, for both radio-bright and radio-dark GRBs. Finally, in agreement with
previous work, we find that very high energy (0.1 - 100 GeV) extended emission
is present in the radio-bright GRB sample only. Our work supports the
possibility that the radio-bright and the radio-dark GRBs originate from
different progenitors.Comment: 19 pages, 9 tables, 17 figure
Effect of single-residue bulges on RNA double-helical structures: crystallographic database analysis and molecular dynamics simulation studies
No full textOxidative Tearing of Graphene Sheets: Insights into the Probable Situations by Computational and Experimental Studies
No full textAqueous oxidation of coal-associated pyrite and standard pyrite mineral towards understanding the depyritization kinetics and acid formations
No full textAbstract In coal mining areas, the ambient atmospheric and aqueous oxidation of pyrite minerals (FeS2) associated with coal as well as the other accompanying strata is significant in understanding the extent of acid mine drainage (AMD), the cause of severe environmental pollution. Therefore, in this paper, the oxidation kinetics of the coal-associated pyrite (CAPy) present in a coal sample (TpHM1) has been studied via aqueous leaching depyritization experiments at variety of temperatures and time intervals without the incorporation of any oxidizer. The outcomes obtained are juxtaposed with the standard pyrite mineral (SPM) oxidation at the same experimental conditions. Also, the coal and SPM slurry residues and filtrates obtained after aqueous leaching at 25 °C and 90 °C for 0 h and 24 h, respectively, were extensively analyzed through high-resolution transmission electron microscopy (HR-TEM), Powder X-ray diffraction (P-XRD), and X-ray-photoelectron spectroscopy (XPS) for evaluation of the mineralogical composition and proportions of iron and sulfur components during progression of the oxidation reaction. Both the reactions obey pseudo first-order kinetics during pyrite (FeS2) oxidation but a significant difference in the experimentally found activation energies (E a) and rate constants (k) values of oxidation kinetics of both CAPy and SPM may be attributed to the varied geochemical compositions of the coal associated pyrite (CAPy). The rate constant for CAPy is much greater than that of SPM implying a higher Ea around 10.838 kJ/mol for SPM as compared to 1.941 kJ/mol for CAPy. The CAPy in coal (TpHM1) is more susceptible to atmospheric oxidation than that of SPM, leading to the formation of acid mine drainage with lower pH. In this paper, the pH values on the basis of stoichiometric pyrite oxidation reaction were calculated and compared with the pH values obtained after aqueous leaching of CAPy to interpret the extent of acid formation and pyrite dissolution. Hence, with the assistance of the current study, further studies on the effects of mineral impurities, whereabouts of pyrite minerals in coal seams, the significance of compositional differences in the CAPy, the effect of metal oxides, and the role of alkalinity producing neutralizing agents of coal in the oxidative dissolution process of pyrite can be investigated
Microbial based natural compounds as potential inhibitors for SARS-CoV-2 Papain-like protease (PLpro): a molecular docking and dynamic simulation study
No full textCOVID-19 (Coronavirus disease of 2019) pandemic is one of the largest health threats the planet has faced in recent decades. Efforts are being continuously made to design a viable drug or a vaccine. Several natural and synthetic molecules are under study for their potency to inhibit viral replication. In order to emphasize the importance of microbial-based natural components in antiviral drug discovery, an attempt has been made through this study to find potential inhibitors for SARS-CoV-2 Papain-Like protease (PLpro) molecule from microbial sources. PLpro, with its multifunctional roles like viral polypeptide proteolysis and suppression of the host's innate immune response, is acting as a potential drug target. The X-ray crystal structure of PLpro and ligand molecules were retrieved from the protein structure database and Npatlas database, respectively. The molecules were screened based on drug likeliness and the pharmacophore model created in reference to a known potent PLpro inhibitor GRL0617. Totally 3272 molecules have undergone the docking process and the complexes of top hits were subjected to 100 ns molecular dynamic simulation. The results showed that Holyrine B, Dihydroarcyriarubin C, Baraphenazine C and 3-hydroxy-3'-N-acetylholyrine A had formed a stable complex in the active site of the PLpro with significant interaction efficiency. Earlier studies showed that Holyrine B could also be a possible inhibitor of the Main protease of SARS-CoV-2, which increases its significance in the process of COVID-19 drug development. In conclusion, these microbial compounds can be considered as possible SARS-CoV-2 inhibitors for further in vitro studies. Communicated by Ramaswamy H. Sarma</p
Polymer Infiltration Into SURMOF Channels Enables Hydrophobic and Solid‐Like Slippery Functional Thin Films
No full textDesigning functional thin films with precisely controlled surface chemistry and smoothness is essential for achieving targeted interfacial properties. Here, we introduce a polymer-chain insertion strategy to fabricate pore-threaded films by grafting uniformly long polymer chains into the vertical channels of surface-mounted metal-organic frameworks (SURMOFs). Using the highly oriented pillared-layer Cu2(bdc)2(dabco) SURMOF grown by layer-by-layer deposition as a crystalline host, infiltration of polymer chains into its nanochannels allows systematic tuning of interfacial chemistry and water wettability. Insertion of hydrophobic n-alkane chains effectively masks the polar framework surface, enhances water stability, and imparts strong hydrophobicity. Polymer incorporation leads to characteristic modifications in the X-ray diffraction pattern, and infrared spectroscopy reveals chain alignment through shifts in CH-stretching modes. Notably, films infiltrated with long tetracontane (C40H82) chains exhibit lubricant-free slippery behavior, enabling water droplets to slide off readily due to the combination of smooth surface morphology and the low surface energy of exposed hydrocarbon segments. This scalable approach provides an internally integrated method for tailoring SURMOF thin-film properties, expanding their applicability in liquid-repellent coatings, anti-fouling surfaces, and separation technologies
