scholarly journals On the emergence of structural complexity in RNA replicators

2017 ◽  
Author(s):  
Carlos G. Oliver ◽  
Vladimir Reinharz ◽  
Jérôme Waldispühl
Keyword(s):  
Large Scale ◽  
Computational Study ◽  
Rna World ◽  
Gc Content ◽  
Structural Complexity ◽  
Molecular Structures ◽  
Stable Complex ◽  
Complex Structures ◽  
Branched Structures ◽  
Stable Structures

AbstractThe RNA world hypothesis relies on the ability of ribonucleic acids to spontaneously acquire complex structures capable of supporting essential biological functions. Multiple sophisticated evolutionary models have been proposed for their emergence, but they often assume specific conditions. In this work we explore a simple and parsimonious scenario describing the emergence of complex molecular structures at the early stages of life. We show that at specific GC-content regimes, an undirected replication model is sufficient to explain the apparition of multi-branched RNA secondary structures – a structural signature of many essential ribozymes. We ran a large scale computational study to map energetically stable structures on complete mutational networks of 50-nucleotide-long RNA sequences. Our results reveal that the sequence landscape with stable structures is enriched with multi-branched structures at a length scale coinciding with the appearance of complex structures in RNA databases. A random replication mechanism preserving a 50% GC-content may suffice to explain a natural enrichment of stable complex structures in populations of functional RNAs. By contrast, an evolutionary mechanism eliciting the most stable folds at each generation appears to help reaching multi-branched structures at highest GC content.

Accelerated Discovery of High-Refractive-Index Polyimides via First-Principles Molecular Modeling, Virtual High-Throughput Screening, and Data Mining

2019 ◽  
Author(s):  
Mohammad Atif Faiz Afzal ◽  
Mojtaba Haghighatlari ◽  
Sai Prasad Ganesh ◽  
Chong Cheng ◽  
Johannes Hachmann
Keyword(s):  
Data Mining ◽  
Refractive Index ◽  
High Throughput ◽  
First Principles ◽  
High Throughput Screening ◽  
Large Scale ◽  
Computational Study ◽  
High Refractive Index ◽  
Structural Features ◽  
Learning Program

<div>We present a high-throughput computational study to identify novel polyimides (PIs) with exceptional refractive index (RI) values for use as optic or optoelectronic materials. Our study utilizes an RI prediction protocol based on a combination of first-principles and data modeling developed in previous work, which we employ on a large-scale PI candidate library generated with the ChemLG code. We deploy the virtual screening software ChemHTPS to automate the assessment of this extensive pool of PI structures in order to determine the performance potential of each candidate. This rapid and efficient approach yields a number of highly promising leads compounds. Using the data mining and machine learning program package ChemML, we analyze the top candidates with respect to prevalent structural features and feature combinations that distinguish them from less promising ones. In particular, we explore the utility of various strategies that introduce highly polarizable moieties into the PI backbone to increase its RI yield. The derived insights provide a foundation for rational and targeted design that goes beyond traditional trial-and-error searches.</div>

scholarly journals Large-Scale, High-Throughput Validation of Short Hairpin RNA Sequences for RNA Interference

2006 ◽  
Vol 11 (3) ◽  
pp. 236-246 ◽  
Author(s):  
Laurence H. Lamarcq ◽  
Bradley J. Scherer ◽  
Michael L. Phelan ◽  
Nikolai N. Kalnine ◽  
Yen H. Nguyen ◽  
...  
Keyword(s):  
High Throughput ◽  
Large Scale ◽  
Strong Support ◽  
Gc Content ◽  
Rapid Identification ◽  
Hairpin Rna ◽  
Rna Sequences ◽  
Short Hairpin ◽  
Short Hairpin Rnas ◽  
Interfering Rna

A method for high-throughput cloning and analysis of short hairpin RNAs (shRNAs) is described. Using this approach, 464 shRNAs against 116 different genes were screened for knockdown efficacy, enabling rapid identification of effective shRNAs against 74 genes. Statistical analysis of the effects of various criteria on the activity of the shRNAs confirmed that some of the rules thought to govern small interfering RNA (siRNA) activity also apply to shRNAs. These include moderate GC content, absence of internal hairpins, and asymmetric thermal stability. However, the authors did not find strong support for positionspecific rules. In addition, analysis of the data suggests that not all genes are equally susceptible to RNAinterference (RNAi).

scholarly journals The Evolution of Isochores: Evidence From SNP Frequency Distributions

Genetics ◽  
2002 ◽  
Vol 162 (4) ◽  
pp. 1805-1810 ◽  
Author(s):  
Martin J Lercher ◽  
Nick G C Smith ◽  
Adam Eyre-Walker ◽  
Laurence D Hurst
Keyword(s):  
Population Genetics ◽  
Large Scale ◽  
Gc Content ◽  
Nucleotide Composition ◽  
Compositional Variation ◽  
Mutation Bias ◽  
Single Nucleotide ◽  
Frequency Distributions ◽  
Noncoding Regions ◽  
Standard Population

AbstractThe large-scale systematic variation in nucleotide composition along mammalian and avian genomes has been a focus of the debate between neutralist and selectionist views of molecular evolution. Here we test whether the compositional variation is due to mutation bias using two new tests, which do not assume compositional equilibrium. In the first test we assume a standard population genetics model, but in the second we make no assumptions about the underlying population genetics. We apply the tests to single-nucleotide polymorphism data from noncoding regions of the human genome. Both models of neutral mutation bias fit the frequency distributions of SNPs segregating in low- and medium-GC-content regions of the genome adequately, although both suggest compositional nonequilibrium. However, neither model fits the frequency distribution of SNPs from the high-GC-content regions. In contrast, a simple population genetics model that incorporates selection or biased gene conversion cannot be rejected. The results suggest that mutation biases are not solely responsible for the compositional biases found in noncoding regions.

scholarly journals Photoprotective Properties of Eumelanin: Computational Insights into the Photophysics of a Catechol:Quinone Heterodimer Model System

Photochem ◽  
2021 ◽  
Vol 1 (1) ◽  
pp. 26-37
Author(s):  
Victoria C. Frederick ◽  
Thomas A. Ashy ◽  
Barbara Marchetti ◽  
Michael N. R. Ashfold ◽  
Tolga N. V. Karsili
Keyword(s):  
Ground State ◽  
Sandwich Structure ◽  
Computational Study ◽  
Minimum Energy ◽  
Carbonyl Oxygen ◽  
Model System ◽  
Molecular Structures ◽  
Uv Damage ◽  
Chromosomal Dna ◽  
Relevant Model

Melanins are skin-centered molecular structures that block harmful UV radiation from the sun and help protect chromosomal DNA from UV damage. Understanding the photodynamics of the chromophores that make up eumelanin is therefore paramount. This manuscript presents a multi-reference computational study of the mechanisms responsible for the experimentally observed photostability of a melanin-relevant model heterodimer comprising a catechol (C)–benzoquinone (Q) pair. The present results validate a recently proposed photoinduced intermolecular transfer of an H atom from an OH moiety of C to a carbonyl-oxygen atom of the Q. Photoexcitation of the ground state C:Q heterodimer (which has a π-stacked “sandwich” structure) results in population of a locally excited ππ* state (on Q), which develops increasing charge-transfer (biradical) character as it evolves to a “hinged” minimum energy geometry and drives proton transfer (i.e., net H atom transfer) from C to Q. The study provides further insights into excited state decay mechanisms that could contribute to the photostability afforded by the bulk polymeric structure of eumelanin.

scholarly journals A large-scale computational study of inhibitor risk in non-severe haemophilia A

2014 ◽  
Vol 168 (3) ◽  
pp. 413-420 ◽  
Author(s):  
Adrian J. Shepherd ◽  
Stuart Skelton ◽  
Clare E. Sansom ◽  
Keith Gomez ◽  
David S. Moss ◽  
...  
Keyword(s):  
Large Scale ◽  
Computational Study ◽  
Haemophilia A ◽  
Severe Haemophilia

Drag Coefficients of Vertically-Mounted Full-Scale Blue Mussel Dropper Lines

2018 ◽  
Author(s):  
Arndt Hildebrandt ◽  
Jannis Landmann ◽  
Thorsten Ongsiek ◽  
Nils Goseberg
Keyword(s):  
Large Scale ◽  
Blue Mussel ◽  
Offshore Structures ◽  
Develop Model ◽  
Complex Structures ◽  
Marine Aquaculture ◽  
Drag Coefficients ◽  
Blue Mussels ◽  
Three Samples ◽  
Physical Testing

Developments in marine aquaculture in the last 30 years indicate that the bivalve-related industry is feasible offshore and that opportunities for large-scale, industrious production of shellfish stock exists. The objective of the project “CAWX1607” is to develop, model and test such systems. However, the forces acting on suspension cultures, the most likely form of marine farm systems are unknown. Here, drag coefficients provide an efficient approach for the calculation of arbitrary complex structures by using the Morison equation. The CD-coefficients take into account vortex shedding effects as well as the surface roughness of the structure. This paper reports on developed and conducted tests at the medium wave and towing tank “Schneiderberg” (WKS) at the Ludwig-Franzius-Institute for Hydraulic, Estuarine and Coastal Engineering of the Leibniz University Hanover, Germany. The tests were conducted for current velocities between 0.25–1.0 m/s for three samples of blue-lipped mussel specimens. During physical testing the forces and moments in x-, y- and z-direction, the elevation of the water surface, a velocity profile in the vicinity of the live-blue mussels, as well as the velocities of the towing carriage were recorded. The developed methodology, data treatment as well as the resulting CD-coefficients are presented. Further, the CD-coefficients obtained are presented in the context of natural variation of living structures and discussed in comparison to CD—curve characteristics of offshore structures, e.g. rough cylinders.

Shock Mitigation by Energy Reversal to the High Frequency Modes

2014 ◽  
Author(s):  
Mohammad A. AL-Shudeifat ◽  
Alexander F. Vakakis ◽  
Lawrence A. Bergman
Keyword(s):  
High Frequency ◽  
Large Scale ◽  
Computational Study ◽  
Dynamic Structure ◽  
Frequency Mode ◽  
Frame Structure ◽  
Shock Energy ◽  
Modal Damping ◽  
Shock Mitigation ◽  
High Frequency Modes

In this computational study, a light-weight dynamic device is investigated for passive energy reversal from the lowest frequency mode to the high frequency modes of a large-scale frame structure for rapid shock mitigation. The device is based on the single-sided vibro-impact mechanism. It has two functions for passive energy transfer: a nonlinear energy sink (NES) for local energy dissipation and an energy pump to high frequency modes where a significant amount of the shock energy is rapidly dissipated. As a result, a significant portion of the shock energy induced into the linear dynamic structure can be passively reversed from the lowest frequency mode to the high frequency modes and rapidly dissipated by their modal damping. The amount of the energy dissipated by the modal damping of the high frequency modes can be controlled by the amount of inherent damping in the device. Ideally, the device can passively reverse up to 80% of the input shock energy from the lowest frequency mode to the high frequency modes when its damping is assumed to be zero and its impact coefficient of restitution is equal to unity. The shock energy redistribution between this device and the high frequency modes is found to be efficient for rapid shock mitigation in the considered 9-story dynamic structure.

scholarly journals On local aromaticity of selected model aza-[n]circulenes (n = 6, 7, 8 and 9): Density functional theoretical study

2019 ◽  
Vol 12 (1) ◽  
pp. 70-81
Author(s):  
Denisa Cagardová ◽  
Vladimír Lukeš ◽  
Ján Matúška ◽  
Peter Poliak
Keyword(s):  
Density Functional ◽  
Computational Study ◽  
Molecular Structures ◽  
Functional Theory ◽  
Structure Of Molecules ◽  
Planar Molecules ◽  
P Type ◽  
Structural Indices ◽  
Lowest Unoccupied Molecular Orbitals ◽  
Local Aromaticity

Abstract A computational study using density functional theory is reported for selected model aza[n]circulenes (n = 6, 7, 8 and 9) and their derivatives consisting of pyrrole and benzene units. Local aromaticity of central rings was discussed and analyzed using theoretical structural indices. Depending on their molecular structures, energies of the highest occupied and lowest unoccupied molecular orbitals change from –5.23 eV to –4.08 eV and from –1.97 eV to –0.41 eV, respectively. Based on B3LYP calculated optimal geometries, electronic structure of molecules and their charge transport properties resulted in the suggestion of three planar molecules containing three or four pyrrole units as potential candidates for p-type semiconductors. Hole drift mobilities for ideal stacked dimers of these potential semiconductors were calculated and they range from 0.94 cm2·V−1·s−1 to 7.33 cm2·V−1·s−1.

scholarly journals Dissimilar Ligands Bind in a Similar Fashion: A Guide to Ligand Binding-Mode Prediction with Application to CELPP Studies

2021 ◽  
Vol 22 (22) ◽  
pp. 12320
Author(s):  
Xianjin Xu ◽  
Xiaoqin Zou
Keyword(s):  
Molecular Similarity ◽  
Complex Structure ◽  
Binding Mode ◽  
Molecular Structures ◽  
Complex Structures ◽  
Binding Modes ◽  
Ligand Complex ◽  
Systematic Analysis ◽  
Binding Mode Prediction ◽  
Similarity Principle

The molecular similarity principle has achieved great successes in the field of drug design/discovery. Existing studies have focused on similar ligands, while the behaviors of dissimilar ligands remain unknown. In this study, we developed an intercomparison strategy in order to compare the binding modes of ligands with different molecular structures. A systematic analysis of a newly constructed protein–ligand complex structure dataset showed that ligands with similar structures tended to share a similar binding mode, which is consistent with the Molecular Similarity Principle. More importantly, the results revealed that dissimilar ligands can also bind in a similar fashion. This finding may open another avenue for drug discovery. Furthermore, a template-guiding method was introduced for predicting protein–ligand complex structures. With the use of dissimilar ligands as templates, our method significantly outperformed the traditional molecular docking methods. The newly developed template-guiding method was further applied to recent CELPP studies.

Structural elaboration in police organizations: an exploration

2017 ◽  
Vol 40 (2) ◽  
pp. 351-365 ◽  
Author(s):  
Alicia L. Jurek ◽  
Matthew C. Matusiak ◽  
Randa Embry Matusiak
Keyword(s):  
Large Scale ◽  
Structural Complexity ◽  
Essential Elements ◽  
Multiple Time ◽  
Police Departments ◽  
Content Type ◽  
Police Organizations ◽  
The Usa ◽  
Multiple Time Points ◽  
American Police

Purpose The current research explores the structural elaboration of municipal American police organizations, specifically, the structural complexity of police organizations and its relationship to time. The purpose of this paper is to describe and test essential elements of the structural elaboration hypothesis. Design/methodology/approach The authors explore the structural elaboration hypothesis utilizing a sample of 219 large police departments across the USA. Data are drawn from multiple waves of the Law Enforcement Management and Administrative Statistics survey and are analyzed using tobit and OLS regression techniques. Findings While there is some evidence that police departments are becoming more elaborate, little evidence for the structural elaboration hypothesis as a function of time is found. Originality/value This project is the first to specifically explore the structural elaboration hypothesis across multiple time points. Additionally, results highlight structural trends across a panel of large American police organizations and provide potential explanations for changes. Suggestions for large-scale policing data collection are also provided.

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