1,097 research outputs found
Dataset in support of the Southampton Doctoral Thesis 'Structure-based modelling of LK peptides in complex with AntagomiR-138 RNA
No full textDataset of production runs and results in support of doctoral thesis: "Structure-Based Modelling of LK Peptides in Complex with AntagomiR-138 RNA"
This dataset is 111 GB and available on request only due to size.
Please complete and return the form https://library.soton.ac.uk/datarequest to [email protected]
</span
Structure-based modelling of LK peptides in complex with antagomiR-138 RNA
No full textRNA is a multipotent polymer of great biological and engineering interest. microRNA mimics have revolutionized the manipulation of gene expression and are being explored as next-generation therapeutics. Despite their high versatility and specificity, their weak pharmacokinetic profile poses serious limitations, that could be bypassed by using biocompatible delivery vectors, such as cell-penetrating peptides (CPPs). Recently, the potent therapeutic microRNA antagonist antagomiR-138 has been successfully delivered using the pH-responsive, histidine-containing CPP LKH-stEK, both in in vivo and in vitro models of glioma. This CPP vector confers high target silencing, albeit with suboptimal complex formation efficiency and cell-penetrating profile, requiring the use of higher concentrations of peptide to achieve the optimal therapeutic effect. In this work, a novel multistage workflow is presented for the sequence-to-structure investigation of antagomiR-138—LKH-stEK nanocomplexes, and the design of new LKH-stEK analogues.In the first stage, the ab initio modelling of the currently unknown RNA and CCP structures was undertaken, using extensive multi-μs enhanced sampling simulations, in combination with knowledge-based and homology modelling tools, to thoroughly investigate the conformational spaces of interest. This process revealed the existence of multiple α-helical, and partially helical conformations for LKH-stEK-like peptides, that are stabilized to various degrees depending on the type of residues at positions 3, 6, and 9 of the 16-mer CPP. Additionally, the protonation of specific histidines of LKH-stEK was found to regulate the helical content of the CPP, suggesting a potential mechanisms for pH-triggered RNA release. For the 23-mer RNA, a parsimonious ensemble of alternative conformations, representing the highly variable hairpin-like predicted structure, was derived after μs-long enhanced sampling simulations under a carefully selected all-atom force field.In the second stage, RNA-CPP aggregates were produced through self-assembling simulations of large-scale systems containing a range of experimentally relevant RNA:CPP ratios (1:5 to 1:50). This thermodynamically-consistent process resulted in the formation of potential nanocomplex precursors with diverse interaction patterns between monomers, shedding light on previously unexplored structural details of these complex delivery systems. To address this complexity, a novel Python-based interaction analysis tool, capable of summarizing widely different intermolecular interactions within aggregates, was developed. This tool evaluates i) the importance of individual residues in relation to properties of interest (e.g. monomer binding) and ii) the different binding modes exhibited by monomers within aggregates, accounting both for local (molecule-based) and global (aggregate-wide) interaction patterns observed in simulation trajectories.Finally, based on the interaction patterns and hotspots of LKH-stEK-like peptides correlated with high complex formation efficiency and cell-penetrating ability, as well as prior information from the CPP design literature, three new targeted designs of LKH-stEK -namely L1W, G16W, and G16A- were proposed to improve specific aspects of the RNA- and peptide-binding capabilities of the lead CPP. Subsequent modelling and simulations of the new designs confirmed the initial hypotheses, further resulting in aggregates with new structural characteristics, making them interesting targets for further experimental investigation and development
Benchmarking RNA all-atom force fields using a set of diverse hairpin motifs
No full text<p><span>Ribonucleic acid (RNA) is a versatile polymer of great biological and engineering interest. Computer simulations that investigate the structure and dynamics of these molecules are powerful tools for understanding and manipulating their physical properties. Despite the progress made towards predictive modeling, many physicochemical aspects remain elusive. Modeling the structural dynamics of RNA is particularly challenging, owing mostly to the flexible, polyanionic backbone and the many polarizable moieties. Several empirical all-atom RNA force fields (FFs) have been developed over the last two decades to address this challenge, albeit with limited reported success. In addition, the sampling profile of such FFs has rarely been explored in detail for RNAs larger than tetranucleotides. This study addresses this issue by benchmarking four state-of-the-art FFs against four full-sequence RNA hairpins, of varying conformational stability, that incorporate a wide range of structural characteristics. Mutli-μs enhanced sampling simulations, starting from distinct and independent conformations, generated well-converged ensembles of loop conformations, enabling an accurate assessment of FF performance. Beyond the robust description of loop conformations, backbone dihedrals, sugar puckers, and contact profiles were thoroughly analyzed and compared to experimental data. Overall, none of the studied FFs was found to quantitatively agree with the available NMR ensembles. Despite this discrepancy, we propose that some FFs might be more appropriate when non-canonical base-pairing or base-backbone interactions are involved. Lastly, we note that different FFs sample significantly different conformational spaces for most cases, making the choice of an appropriate RNA FF non-trivial.</span></p>
Babel, or the local distortion of the Greek language
No full textTitle: Βαβυλωνία ἤ ἡ κατά τόπους διαφθορά τῆς ἑλληνικῆς γλώσσας. Κωµωδία (Babel, or the local distortion of the Greek language: A comedy) Originally published: Ναύπλιο (Nafplio), Τυπογραφεῖsο Κωνσταντίνου Τόµπρα ἐκ Κυδωνιῶν καὶ Κωνσταντίνου Ἰωαννίδη ἐκ Σµύρνης, 1836 Language: Greek The excerpt used is from D. C. Vyzantios, Βαβυλωνία, introduction by Spyros Evangelatos (Athens: Εστία, 1993), pp.1–3. About the author Dimitrios Vyzantios (pseudonym of Dimitrios K. Hatziaslanis) [1790, Constantin..
Group 8: Challenge: Event detection in nanopore data
No full textTranslocation of DNA molecules through special membrane nanopores- under the application of electric current- results in change of the nanopore current [1,2]. The produced signals have characteristic patterns that depend on the type of event that takes place, i.e. the configuration of the DNA molecule that passes through the pore. The focus of this challenge is the development of methods for: 1. detecting the events 2. classifying the events based on the signal pattern 3. finding an appropriate measure for quantifying the success of the model The provided data for this challenge consist of nine simulation sets produced by tuning the signal-to-noise ratio (SNR) at 100, 50, 10, 5, 4, 3, 2, 1.5, and 1. Each set (same SNR level) consists of five simulations of electric current time series, resulting in a total of forty-five simulations. An example plot of the data with the maximum SNR of 100 is shown in Figure 1, where the spikes in the data correspond to events. Zooming in on the graph at each of these spikes, it is possible to identify a range of three patterns corresponding to the different classes of event. As the SNR decreases, the true signals become more difficult to distinguish from the natural variation resulting from the noise. Therefore, devising a method to identify events when the SNR is low is a particularly important challenge
Dimitrios Tsamis Karatasos : a symbol of Greek, Serbian and Bulgarian friendship
No full textTwo Serbian texts extol the contribution of Dimitrios Tsamis Karatasos to the Balkan joint effort to throw off the Ottoman yoke. These texts are analysed by the author within the historical framework of their period, so that the man’s personality and work may be accurately evaluated from a fresh viewpoint. More specifically, the author conducts a research on the tombstone of Dimitrios Tsamis Karatasos, which he discovered himself at Naoussa, and the octet engraved on it, which is also published here. The work is illustrated by seven plates, of which four have not been published previously
The Remains of authoritarianism : bureaucracy and civil society in post-authoritarian Greece
No full textDimitrios A. Sotiropoulos. 30 cm. He presented this paper at a seminar held at the Center on October 21, 1994. - T.p. Includes bibliographical references (p. 31-35
Erratum: Korkovelos, A., et al. The role of open access data in geospatial electrification planning and the achievement of SDG7. An OnSSET-based case study for Malawi. <i>Energies</i> 2019, 12(7), 1395
No full textThe authors wish to make a change in author names (adding new author—Dimitrios Mentis) to this paper
The Exemplary Life of Dimitrios Vikelas (1835-1908)
No full textThis paper describes the "satisfying curve" of Dimitrios Vikelas' life journey, starting from Syros in 1835, moving via Constantinople, Odessa, and Syros again, to London, Paris and finally Athens. It explores Vikelas' multiple aspects, as merchant, writer, traveller, lecturer and essayist, Olympic founder, educationalist, book collector and philanthropist, all of which were united in the public-spirited man of letters (logios). It sets Vikelas in the context of the Greek commercial diaspora, the world of the London expatriate Greek community, and the dynamic society of late nineteenth-century Athens, beginning in the 1870s to act as a magnet to Greek expatriates. The author stresses two qualities of Vikelas: his belief in the idea of a progressive Greek state marked by advances in education, culture, tourism and standards of public life; and the self-awareness and experience which inform his autobiographical writings, not only his memoir My Life but also his last such work, The War of 1897
Turbulence structure and flow resistance in oscillatory boundary layer flows
No full textSubmission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2022-12-01The student, Dimitrios Fytanidis, accepted the attached license on 2020-12-01 at 15:14.The student, Dimitrios Fytanidis, submitted this Dissertation for approval on 2020-12-01 at 15:22.This Dissertation was approved for publication on 2020-12-03 at 08:17.DSpace SAF Submission Ingestion Package generated from Vireo submission #16014 on 2021-03-04 at 16:32:49Made available in DSpace on 2021-03-05T21:45:43Z (GMT). No. of bitstreams: 15
FYTANIDIS-DISSERTATION-2020.pdf: 35582374 bytes, checksum: 7b9c9c750d2433e542eaf143a5250e52 (MD5)
Chapter 3 video 1.mp4: 224359 bytes, checksum: 6afa84d5c6e82411e07f0511842c0a45 (MD5)
Chapter 3 video 2.mp4: 235936 bytes, checksum: 67eb7a455fb5fabea8be13df717776e4 (MD5)
Chapter 3 video 3.mp4: 229067 bytes, checksum: c935df21c9eafbe725b9242f872ce935 (MD5)
Chapter 3 video 4.mp4: 234118 bytes, checksum: 25f0589bd05aefb66ca37a8bb6328ae9 (MD5)
Chapter 3 video 5.mp4: 236618 bytes, checksum: 9fd9cf1dd3c46235f634db8e78b204f4 (MD5)
Chapter 3 video 6.mp4: 299851 bytes, checksum: b92ed9f2c8fc2eb08fdc3b415a0a01bb (MD5)
Chapter 3 video 7.mp4: 500994 bytes, checksum: 8e483049044150c77b60f4c36d846ada (MD5)
Chapter 3 video 8.mp4: 440636 bytes, checksum: 32f7a6af91937d0494abaeb85b9b693e (MD5)
Chapter 3 video 9.mp4: 405371 bytes, checksum: 4483e992585bad044eb21d13dd64cbad (MD5)
Chapter 4 video 1.mp4: 11721062 bytes, checksum: 16f6a8e700a78c59c9179829882b2b3c (MD5)
Chapter 4 video 2.mp4: 24428028 bytes, checksum: b11b5fcf99ef1f088f0cbd0fd681f914 (MD5)
Chapter 4 video 3.mp4: 61362991 bytes, checksum: 75b033db9ab7d86256113f026636a85a (MD5)
Copyrights.pdf: 1168055 bytes, checksum: 92c97ab45ac524ef66a379b6ba515d32 (MD5)
LICENSE.txt: 4216 bytes, checksum: 8139025cc39d2751fa86c850a031efc3 (MD5)
Previous issue date: 2020-12-03Embargo set by: Seth Robbins for item 117320
Lift date: 2023-03-05T21:45:47Z
Reason: Author requested closed access (OA after 2yrs) in Vireo ETD systemEmbargo set by: Seth Robbins for item 117320
Lift date: 2023-03-05T21:47:41Z
Reason: Author requested closed access (OA after 2yrs) in Vireo ETD systemAuthor requested closed access (OA after 2yrs) in Vireo ETD systemLimite
- …
