Computational Investigation of Structure-Function Relationship in Fluorine-Functionalized MOFs for PFOA Capture from Water

A strategy that can be used to develop metal-organic frameworks (MOFs) to capture per- and poly-fluoroalkyl substances (PFAS) from water is functionalizing them with fluorine moieties. We investigated different fluorine-functionalization strategies and their performance in removing PFAS from water using molecular simulations. Perfluorooctanoic acid (PFOA), one of the most widely encountered PFAS in water sources, was used as the probe molecule. Our simulations show that fluorine functionalization by incorporating fluorinated anions as bridging ligands in MOFs creates additional binding sites for PFOA; however, the same sites also attract water molecules, which casts doubt on their potential use. In contrast, trifluoromethyl or fluorine substitution of the MOF ligands results in higher hydrophobicity. However, the pores fluorinated with this method should have the optimum size to accommodate PFOA. Likewise, post-synthetic fluorine functionalization of MOFs through grafting of perfluorinated alkanes showed increased PFOA affinity. Fluorine-functionalized MOFs with high hydrophobicity and optimized pore sizes can effectively capture PFOA from water at very low concentrations of PFOA

Rapid and Efficient Removal of Perfluorooctanoic Acid from Water with Fluorine-Rich Calixarene-Based Porous Polymers

On account of its nonbiodegradable nature and persistence in the environment, perfluorooctanoic acid (PFOA) accumulates in water resources and poses serious environmental issues in many parts of the world. Here, we present the development of two fluorine-rich calix[4]arene-based porous polymers, FCX4-P and FCX4-BP, and demonstrate their utility for the efficient removal of PFOA from water. These materials featured Brunauer–Emmett–Teller (BET) surface areas of up to 450 m^{2} g^{-1}, which is slightly lower than their nonfluorinated counterparts (up to 596 m^{2} g^{-1}). FCX4-P removes PFOA at environmentally relevant concentrations with a high rate constant of 3.80 g mg^{-1} h^{-1} and reached an exceptional maximum PFOA uptake capacity of 188.7 mg g^{-1}. In addition, it could be regenerated by simple methanol wash and reused without a significant decrease in performance

Fine-Tuning NER with spaCy for Transliterated Entities Found in Digital Collections From the Multilingual Persian Gulf

Text recognition technologies increase access to global archives and make possible their computational study using techniques such as Named Entity Recognition (NER). In this paper, we present an approach to extracting a variety of named entities (NE) in unstructured historical datasets from open digital collections dealing with a space of informal British empire: the Persian Gulf region. The sources are largely concerned with people, places and tribes as well as economic and diplomatic transactions in the region. Since models in state-of-the-art NER systems function with limited tag sets and are generally trained on English-language media, they struggle to capture entities of interest to the historian and do not perform well with entities transliterated from other languages. We build custom spaCy-based NER models trained on domain-specific annotated datasets. We also extend the set of named entity labels provided by spaCy and focus on detecting entities of non-Western origin, particularly from Arabic and Farsi. We test and compare performance of the blank, pre-trained and merged spaCy-based models, suggesting further improvements. Our study makes an intervention into thinking beyond Western notions of the entity in digital historical research by creating more inclusive models using non-metropolitan corpora in English

Refolding upon force quench and pathways of mechanical and thermal unfolding of ubiquitin

The refolding from stretched initial conformations of ubiquitin (PDB ID: 1ubq) under the quenched force is studied using the Go model and the Langevin dynamics. It is shown that the refolding decouples the collapse and folding kinetics. The force quench refolding times scale as tau_F ~ exp(f_q*x_F/k_B*T), where f_q is the quench force and x_F = 0.96 nm is the location of the average transition state along the reaction coordinate given by the end-to-end distance. This value is close to x_F = 0.8 nm obtained from the force-clamp experiments. The mechanical and thermal unfolding pathways are studied and compared with the experimental and all-atom simulation results in detail. The sequencing of thermal unfolding was found to be markedly different from the mechanical one. It is found that fixing the N-terminus of ubiquitin changes its mechanical unfolding pathways much more drastically compared to the case when the C-end is anchored. We obtained the distance between the native state and the transition state x_UF=0.24 nm which is in reasonable agreement with the experimental data.Comment: 35 pages, 15 figures, 1 tabl

Single-molecule pulling: phenomenology and interpretation

Single-molecule pulling techniques have emerged as versatile tools for probing the noncovalent forces holding together the secondary and tertiary structure of macromolecules. They also constitute a way to study at the single-molecule level processes that are familiar from our macroscopic thermodynamic experience. In this Chapter, we summarize the essential phenomenology that is typically observed during single-molecule pulling, provide a general statistical mechanical framework for the interpretation of the equilibrium force spectroscopy and illustrate how to simulate single-molecule pulling experiments using molecular dynamics.Comment: arXiv admin note: text overlap with arXiv:0908.220

Mechano-chemical kinetics of DNA replication: identification of the translocation step of a replicative DNA polymerase

[EN] During DNA replication replicative polymerases move in discrete mechanical steps along the DNA template. To address how the chemical cycle is coupled to mechanical motion of the enzyme, here we use optical tweezers to study the translocation mechanism of individual bacteriophage Phi29 DNA polymerases during processive DNA replication. We determine the main kinetic parameters of the nucleotide incorporation cycle and their dependence on external load and nucleotide (dNTP) concentration. The data is inconsistent with power stroke models for translocation, instead supports a loose-coupling mechanism between chemical catalysis and mechanical translocation during DNA replication. According to this mechanism the DNA polymerase works by alternating between a dNTP/PPi-free state, which diffuses thermally between pre- and post-translocated states, and a dNTP/PPi-bound state where dNTP binding stabilizes the post-translocated state. We show how this thermal ratchet mechanism is used by the polymerase to generate work against large opposing loads (~50 pN).We thank Stephan Grill laboratory (MPI-CBG, Dresden) for help with data collection and E. Galburt, M. Manosas and M. De Vega for critical reading of the manuscript. Spanish Ministry of Economy and Competitiveness [BFU2011-29038 to J.L.C., BFU2013-44202 to J.M.V., BFU2011-23645 to M.S., FIS2010-17440, GR35/10-A920GR35/10-A-911 to F.J.C., MAT2013-49455-EXP to J.R.A.-G. and BFU2012-31825 to B.I.]; Regional Government of Madrid [S2009/MAT 1507 to J.L.C. and CDS2007-0015 to M.S.]; European Molecular Biology Organization [ASTF 276-2012 to J.M.L.]. Funding for open access charge: Spanish Ministry of Economy and Competitiveness [BFU2012-31825 to B.I.].Morin, J.; Cao, F.; Lázaro, J.; Arias-Gonzalez, JR.; Valpuesta, J.; Carrascosa, J.; Salas, M.... (2015). 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The EMBO Journal, 25(15), 3458-3468. doi:10.1038/sj.emboj.7601211Zhang, H., Cao, W., Zakharova, E., Konigsberg, W., & De La Cruz, E. M. (2007). Fluorescence of 2-aminopurine reveals rapid conformational changes in the RB69 DNA polymerase-primer/template complexes upon binding and incorporation of matched deoxynucleoside triphosphates. Nucleic Acids Research, 35(18), 6052-6062. doi:10.1093/nar/gkm587Wang, W., Wu, E. Y., Hellinga, H. W., & Beese, L. S. (2012). Structural Factors That Determine Selectivity of a High Fidelity DNA Polymerase for Deoxy-, Dideoxy-, and Ribonucleotides. Journal of Biological Chemistry, 287(34), 28215-28226. doi:10.1074/jbc.m112.366609Berezhna, S. Y., Gill, J. P., Lamichhane, R., & Millar, D. P. (2012). Single-Molecule Förster Resonance Energy Transfer Reveals an Innate Fidelity Checkpoint in DNA Polymerase I. Journal of the American Chemical Society, 134(27), 11261-11268. doi:10.1021/ja3038273Hariharan, C., Bloom, L. B., Helquist, S. A., Kool, E. 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Journal of Biological Chemistry, 276(14), 10824-10831. doi:10.1074/jbc.m008680200Rothwell, P. J., Mitaksov, V., & Waksman, G. (2005). Motions of the Fingers Subdomain of Klentaq1 Are Fast and Not Rate Limiting: Implications for the Molecular Basis of Fidelity in DNA Polymerases. Molecular Cell, 19(3), 345-355. doi:10.1016/j.molcel.2005.06.032Patel, S. S., Wong, I., & Johnson, K. A. (1991). Pre-steady-state kinetic analysis of processive DNA replication including complete characterization of an exonuclease-deficient mutant. Biochemistry, 30(2), 511-525. doi:10.1021/bi00216a029Luo, G., Wang, M., Konigsberg, W. H., & Xie, X. S. (2007). Single-molecule and ensemble fluorescence assays for a functionally important conformational change in T7 DNA polymerase. Proceedings of the National Academy of Sciences, 104(31), 12610-12615. doi:10.1073/pnas.0700920104Joyce, C. M., & Benkovic, S. J. (2004). DNA Polymerase Fidelity:  Kinetics, Structure, and Checkpoints†. 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Trigger loop dynamics mediate the balance between the transcriptional fidelity and speed of RNA polymerase II. Proceedings of the National Academy of Sciences, 109(17), 6555-6560. doi:10.1073/pnas.1200939109Bar-Nahum, G., Epshtein, V., Ruckenstein, A. E., Rafikov, R., Mustaev, A., & Nudler, E. (2005). A Ratchet Mechanism of Transcription Elongation and Its Control. Cell, 120(2), 183-193. doi:10.1016/j.cell.2004.11.045Bai, L., Fulbright, R. M., & Wang, M. D. (2007). Mechanochemical Kinetics of Transcription Elongation. Physical Review Letters, 98(6). doi:10.1103/physrevlett.98.068103Abbondanzieri, E. A., Greenleaf, W. J., Shaevitz, J. W., Landick, R., & Block, S. M. (2005). Direct observation of base-pair stepping by RNA polymerase. Nature, 438(7067), 460-465. doi:10.1038/nature04268Dangkulwanich, M., Ishibashi, T., Liu, S., Kireeva, M. L., Lubkowska, L., Kashlev, M., & Bustamante, C. J. (2013). 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Characterization of the kinetic and thermodynamic landscape of RNA folding using a novel application of isothermal titration calorimetry

A novel isothermal titration calorimetry (ITC) method was applied to investigate RNA helical packing driven by the GAAA tetraloop–receptor interaction in magnesium and potassium solutions. Both the kinetics and thermodynamics were obtained in individual ITC experiments, and analysis of the kinetic data over a range of temperatures provided Arrhenius activation energies (ΔH‡) and Eyring transition state entropies (ΔS‡). The resulting rich dataset reveals strongly contrasting kinetic and thermodynamic profiles for this RNA folding system when stabilized by potassium versus magnesium. In potassium, association is highly exothermic (ΔH25°C = −41.6 ± 1.2 kcal/mol in 150 mM KCl) and the transition state is enthalpically barrierless (ΔH‡ = −0.6 ± 0.5). These parameters are sigificantly positively shifted in magnesium (ΔH25°C = −20.5 ± 2.1 kcal/mol, ΔH‡ = 7.3 ± 2.2 kcal/mol in 0.5 mM MgCl2). Mixed salt solutions approximating physiological conditions exhibit an intermediate thermodynamic character. The cation-dependent thermodynamic landscape may reflect either a salt-dependent unbound receptor conformation, or alternatively and more generally, it may reflect a small per-cation enthalpic penalty associated with folding-coupled magnesium uptake