21,237 research outputs found
RNA Conformational Ensembles: Narrowing the GAP between Experiments and Simulations with Metadynamics
No full textThe computational study of conformational transitions in nucleic acids still faces many challenges. For example, in the case of single stranded RNA tetranucleotides, agreement between simulations and experiments is not satisfactory due to inaccuracies in the force fields commonly used in molecular dynamics. Improvement of force fields is however hindered by the difficulties of decoupling those errors from the statistical errors caused by insufficient sampling. We here tackle both problems simultaneously by introducing a novel enhancing sampling method and using experimental data to improve RNA force fields.
In this novel method, concurrent well-tempered metadynamics are integrated in a Hamiltonian replica-exchange scheme. The ladder of replicas is built with different strength of the bias potential exploiting the tunability of well-tempered metadynamics so as to scale barriers on individual collective variables [1]. At the same time, the metadynamics algorithm is modified so as to allow enforcing a target distribution of backbone and sugar-base torsion angles taken from experimental structures, using a procedure related to two recently introduced techniques. Replica-exchange simulations of several RNA tetranucleotides with experimental corrections show significantly better agreement with NMR experimental data and suggest a systematic procedure for force field refinement.
[1] Gil-Ley, A.; Bussi, G. J. Chem. Theory Comput. 2015, 11, 1077-1085
Enhanced sampling and force field corrections for RNA oligomers
No full textThe computational study of conformational transitions in nucleic acids still faces many challenges. For example, in the case of single stranded RNA tetranucleotides, agreement between simulations and experiments is not satisfactory due to inaccuracies in the force fields commonly used in molecular dynamics. Improvement of force fields is however hindered by the diiculties of decoupling those errors from the statistical errors caused by insuicient sampling. We here tackle both problems by introducing a novel enhancing sampling method and using experimental data to improve RNA force fields.
In this novel method, concurrent well-tempered metadynamics are integrated in a Hamiltonian replica-exchange scheme. The ladder of replicas is built with different strength of the bias potential exploiting the tunability of well-tempered metadynamics. Using this method, free-energy barriers associated to individual collective variables are significantly reduced compared with simple force-field scaling. The introduced methodology is flexible and allows adaptive bias potentials to be self-consistently constructed for a large number of simple collective variables, such as distances and dihedral angles.
Additionally, a modified metadynamics algorithm is used to calculate correcting potentials designed to enforce distributions of backbone torsion angles taken from experimental structures. Replica-exchange simulations of tetranucleotides including these correcting potentials show significantly better agreement with independent solution experiments for the oligonucleotides containing pyrimidine bases. Although the proposed corrections do not seem to be portable to generic RNA systems, the simulations reveal the importance of the α and ζ backbone angles for the modulation of the RNA conformational ensemble. The correction protocol presented here suggests a systematic procedure for force-field refinement
Enhanced Conformational Sampling using Replica Exchange with Collective-Variable Tempering
No full textThe computational study of conformational transitions in RNA and proteins with atomistic molecular dynamics often requires suitable enhanced sampling techniques.
We here introduce a novel method where concurrent metadynamics are integrated in a Hamiltonian replica-exchange scheme. The ladder of replicas is built with different strength of the bias potential exploiting the tunability of well-tempered metadynamics.
Using this method, free-energy barriers of individual collective variables are significantly reduced compared with simple force-field scaling. The introduced methodology is flexible and allows adaptive bias potentials to be self-consistently constructed for a large number of simple collective variables, such as distances and dihedral angles. The method is tested on alanine dipeptide and applied to the difficult problem of
conformational sampling in a tetranucleotide
Ecologia política tercer trabajo colaborativo Sergio Gil y Alejandro López López
No full text<p>Ecologia política tercer trabajo colaborativo Sergio Gil y Alejandro López López</p>
Combining simulations and solution experiments as a paradigm for RNA force field refinement
No full textRecent computational efforts have shown that the current potential energy models used in molecular dynamics are not accurate enough to describe the conformational ensemble of RNA oligomers and suggest that molecular dynamics should be complemented with experimental data. We here propose a scheme based on the maximum entropy principle to combine simulations with bulk experiments. In the proposed scheme, the noise arising from both the measurements and the forward models used to back-calculate the experimental observables is explicitly taken into account. The method is tested on RNA nucleosides and is then used to construct chemically consistent corrections to the Amber RNA force field that allow a large set of experimental data on nucleosides and dinucleosides to be correctly reproduced. The transferability of these corrections is assessed against independent data on tetranucleotides and displays a previously unreported agreement with experiments. This procedure can be applied to enforce multiple experimental data on multiple systems in a self-consistent framework, thus suggesting a new paradigm for force field refinement. © 2016 American Chemical Societ
Empirical corrections to the Amber RNA force field with Target Metadynamics
No full textThe computational study of conformational transitions in nucleic acids still faces many challenges. For example, in the case of single stranded RNA tetranucleotides, agreement between simulations and experiments is not satisfactory due to inaccuracies in the force fields commonly used in molecular dynamics simulations. We here use experimental data collected from high-resolution X-ray structures to attempt an improvement of the latest version of the AMBER force field. A modified metadynamics algorithm is used to calculate correcting potentials designed to enforce experimental distributions of backbone torsion angles. Replica-exchange simulations of tetranucleotides including these correcting potentials show significantly better agreement with independent solution experiments for the oligonucleotides containing pyrimidine bases. Although the proposed corrections do not seem to be portable to generic RNA systems, the simulations revealed the importance of the α and ζ backbone angles for the modulation of the RNA conformational ensemble. The correction protocol presented here suggests a systematic procedure for force-field refinement
RNA Folding Pathways in Stop Motion
No full textWe introduce a method for predicting RNA folding pathways, with an application to the most important RNA tetraloops. The method is based on the idea that ensembles of three-dimensional fragments extracted from high-resolution crystal structures are heterogeneous enough to describe metastable as well as intermediate states. These ensembles are first validated by performing a quantitative comparison against available solution NMR data of a set of RNA tetranucleotides. Notably, the agreement is better with respect to the one obtained by comparing NMR with extensive all-atom molecular dynamics simulations. We then propose a procedure based on diffusion maps and Markov models that makes it possible to obtain reaction pathways and their relative probabilities from fragment ensembles. This approach is applied to study the helix-to-loop folding pathway of all the tetraloops from the GNRA and UNCG families. The results give detailed insights into the folding mechanism that are compatible with available experimental data and clarify the role of intermediate states observed in previous simulation studies. The method is computationally inexpensive and can be used to study arbitrary conformational transitions
Auto de la Barca del Infierno, de Gil Vicente: Introducción, traducción y notas de Alejandro López Lapeña
No full textEdició de l’obra teatral portuguesa AUTO DE LA BARCA DELINFIERNO de Gil Vicente, a càrrec de Alejandro L. Lapeña, responsable de la introducció, traducció al castellà i les notes, amb el text portugués editat per José Camões i Helena Reis Silva per al Centro de Estudos de Teatro de la Universidade de Lisboa. Edición de la obra portuguesa AUTO DE LA BARCA DEL INFIERNO, de Gil Vicente, a cargo de Alejandro L. Lapeña, responsable de la introducción, la traducción al español y las notas, con el texto portugués editado por José Camões y Helena Reis Silva para el Centro de Estudios Teatrales de la Universidad de Lisboa.  
Auto de la Barca del Infierno, de Gil Vicente: Introducción, traducción y notas de Alejandro López Lapeña
No full textEdició de l’obra teatral portuguesa AUTO DE LA BARCA DELINFIERNO de Gil Vicente, a càrrec de Alejandro L. Lapeña, responsable de la introducció, traducció al castellà i les notes, amb el text portugués editat per José Camões i Helena Reis Silva per al Centro de Estudos de Teatro de la Universidade de Lisboa. Edición de la obra portuguesa AUTO DE LA BARCA DEL INFIERNO, de Gil Vicente, a cargo de Alejandro L. Lapeña, responsable de la introducción, la traducción al español y las notas, con el texto portugués editado por José Camões y Helena Reis Silva para el Centro de Estudios Teatrales de la Universidad de Lisboa.  
Diseño y aplicaciones de sistemas de antenas inteligentes para redes inalámbricas en el contexto de la internet de las cosas
No full text[SPA] Esta tesis doctoral se presenta bajo la modalidad de compendio de publicaciones. Las antenas de onda de fuga (LWA) consisten en una estructura de guía de onda que permite la fuga de parte de la potencia a lo largo de la estructura. Por esta razón, la radiación de la antena se produce por la fuga de energía. Para producir una radiación coherente, es necesario controlar esta tasa de radiación a lo largo de la estructura radiante. Así, ajustando con precisión la tasa de radiación, se controla la forma del diagrama de radiación. Las LWAs han sido ampliamente estudiadas por la comunidad científica debido a sus ventajas, tales como, red de alimentación simple, alta directividad y escaneo en frecuencia pasivo. Sin embargo, presentan ciertas desventajas entre las cuales, la más importante a destacar es el efecto de beam-squinting. Éste se produce por la propiedad dispersiva inherente a este tipo de antenas. Además, presentan dificultades a la hora de generar radiación coherente en las direcciones broadside y endfire, aumentando la complejidad del diseńo para la radiación en dichas direcciones. Las LWA han sido relativamente poco utilizadas en aplicaciones prácticas hasta la fecha, a pesar de sus ventajas. Las pocas aplicaciones en las que se han utilizado son los radares de onda continua modulada en frecuencia y los sistemas de enfoque controlado en frecuencia de campo cercano. Esta tesis propone el uso de las LWAs en aplicaciones prácticas aprovechando las ventajas mencionadas anteriormente y teniendo en cuenta los inconvenientes de este tipo de antenas para que su uso no sea limitado. Recientemente, las LWAs han sido propuestas para aplicaciones de localización de bajo coste, ya que permiten el diseńo de estructuras planas con haces directivos. Además, debido al aumento exponencial del uso de la tecnología, es necesario encontrar nuevas tecnologías para una transmisión de datos mayor, más rápida y más eficiente, manteniendo bajos costes de fabricación. Por lo tanto las LWAs pueden ser una solución crucial al mezclar bajos costes de fabricación, alta integrabilidad en diferentes sistemas debido a su tecnología impresa planar y alta directividad al mismo tiempo que se aprovecha su característica dispersiva que proporciona un escaneo pasivo en frecuencia. En este contexto, la principal aportación de esta Tesis consiste en el estudio, análisis, diseńo e integración de LWAs en aplicaciones reales y prácticas. Esta Tesis presenta las siguientes tres contribuciones principales, definidas en los tres bloques principales de este documento: • Estudio y análisis de LWAs para su uso en sistemas de estimación de dirección de llegada basados en técnicas de amplitud de monopulso. Comparar las características y prestaciones de las LWAs junto con las antenas comerciales más utilizadas. Para ello, diseńar y fabricar las HWM-LWAs con el fin de comparar sus prestaciones con las antenas de panel adquiridas comercialmente. Dado que cada aplicación requiere el diseńo de una HWM-LWA nueva y diferente, estudiar y proponer una técnica eficiente de análisis y diseńo de antenas para obtener fácilmente diagramas de radiación monopulso escaneados en frecuencia. • Una vez analizado que las HWM-LWA son una solución factible para su uso en aplicaciones reales de localización debido a sus diversas ventajas. Integrar las HWM-LWAs diseńadas en sistemas digitales para estimación del ángulo de llegada en interiores. Por lo tanto, diseńar, desarrollar, configurar e integrar las LWAs en diferentes sistemas basados en las bandas de frecuencia Wi-Fi ISM de 2,4 GHz y 5 GHz. Finalmente, comparar los resultados de estimación obtenidos con otras soluciones propuestas para corroborar que los LWAs pueden ser utilizados en aplicaciones reales. • Asimismo, debido a su bajo coste de fabricación y a su principal propiedad de escaneo en frecuencia. Ampliar el uso de las LWAs para la localización angular en redes de sensores inalámbricas (WSN) utilizando la banda de frecuencias UHF de 900 MHz. Utilizando así etiquetas RFID pasivas. También estudiar su aplicabilidad en WSNs utilizando etiquetas LoRa activas. Este documento se presenta como una Tesis por compendio, por lo que se presentarán y explicarán brevemente los 4 artículos de revistas que se han publicado durante el programa de doctorado. Además, también se presentarán algunos artículos de conferencias y otros trabajos en revisión para exponer algunas de las investigaciones que no han sido publicadas en revistas hasta la fecha de depósito de tesis. El documento está organizado como se indica a continuación: En la Introducción, se presenta una contextualización del estado del arte y una explicación rigurosa sobre las LWAs y las aplicaciones anteriormente mencionadas. Las dos partes siguientes se vi dedican a presentar y explicar brevemente los trabajos publicados que contribuyen a esta Tesis. En la parte II, se presentan los cuatro artículos que conforman el compendio. Esto es, el análisis de las LWAs para la estimación de la dirección del ángulo de llegada y la integración de las LWAs en sistemas de localización digital usando el protocolo Wi-Fi en el Capítulo 1, la banda de frecuencias ISM UHF 900 MHz se utiliza junto con los HWM-LWAs en el Capítulo 2, luego se implementa en un sistema en tiempo real para la estimación de la dirección de llegada de múltiples tags pasivos en el Capítulo 3 y la integración de LoRa en el Capítulo 4. Finalmente, en la Parte III, se discuten las conclusiones generales y las futuras líneas de investigación. [ENG] This doctoral dissertation has been presented in the form of thesis by publication. Leaky-Wave Antennas (LWA) consist on a waveguide structure which allows the leakage of part of the power along the structure. For this reason, the radiation of the antenna is produced by the leakage of power. In order to produce coherent radiation, it is necessary to control this leakage rate along the radiating structure. Thus, precisely adjusting the leakage rate, the shape of the radiation pattern is controlled. LWAs have been widely studied by the scientific community due to their advantages, such as, simple feeding network, high directivity and passive frequency-scanning performance. However, they present certain disadvantages among which, the most important to highlight is the beam-squinting effect. TThis is due to the inherent dispersion property of this type of antenna. In addition, LWAs present difficulties when generating coherent radiation in broadside and endfire directions, increasing the complexity of the design for radiation in these directions. LWAs have been relatively unused in practical applications to date, despite of their benefits. The few applications in which they have been used are frequency modulated continuous wave radars and near-field frequency controlled focusing systems.This thesis proposes the use of LWAs in practical applications by exploiting the advantages mentioned above while taking into account the drawbacks of this type of antennas so that their use is not limited. Recently, LWAs have been proposed for low-cost localization applications, as they allow the design of planar structures with directive beams. In addition, due to the exponential increase in the use of technology, it is necessary to find new technologies for higher, faster and more efficient data transmission while maintaining low manufacturing costs. Therefore, LWAs can be a crucial solution mixing low manufacturing costs, high integrability in different systems due to their planar printed technology and high directivity while taking advantage of their dispersive characteristic that provides passive frequency scanning. In this context, the main contribution of this Thesis consist of the study, analysis, design and integration of LWAs in real and practical applications. This Thesis presents the following three main contributions, defined in the three main blocks of this document: • Study and analysis of LWAs for its use in direction of arrival estimation systems based on monopulse amplitude techniques. Compare the characteristics and performance of LWAs along with widely used commercial antennas. For this purpose, design and manufacture the HWM-LWAs in order to compare their performance with commercially acquired panel antennas. Since each application requires the design of a new and different HWM-LWA, a main objective of this block is to study and propose an efficient antenna analysis and design technique to facilitate obtaining frequency-scanned monopulse patterns. • Once analyzed that LWAs are a feasible solution for its use in real localization applications due to their several advantages, integrate the designed half-width microstrip (HWM-LWAs) in digital indoor angle-of-arrival estimation systems. Therefore, design, develop, configure and integrate LWAs in different systems based on the Wi-Fi ISM 2.4 GHz and 5 GHz frequency bands. Finally, compare the obtained estimation results with other proposed solutions to corroborate that LWAs can be used in real applications. • Extending the use of antennas for angular localization in sensor networks using the 900 MHz UHF frequency band: the main properties of low manufacturing cost and passive frequency beam scanning can be used in other applications. Thus, the localization estimation of passive RFID tags is studied, as well as their application in Wireless Sensor Networks (WSNs) using active tags with LORA technology. This document is presented as a Thesis by compilation, so the 4 journal articles that have been published during the Ph.D program will be presented and briefly explained. Besides, some conference articles and other work under review will be also presented to expose some of the research that has not been published in journals. The document is organized as outlined hereafter: In Part I, a state-of-the-art contextualization, a rigorous explanation about LWAs and the previous applications mentioned above is presented. The next two parts are dedicated to present and briefly explain the published works included in this Thesis and their main contributions. In Part II the explanation of the four papers which compose the compendium are presented. This is, LWAs analysis for direction of arrival estimation and the integration of LWAs in digital Wi-Fi localization systems in chapter 1, the UHF 900 MHz ISM frequency band is used in conjunction with HWM-LWAs in chapter 2, then, it is implemented in a real time system for direction of arrival estimation of multi RFID tags in chapter 3 and LoRa integration in chapter 4. Finally, in Part III, the overall conclusions and the future research lines are discussed.Escuela Internacional de Doctorado de la Universidad Politécnica de CartagenaPrograma Doctorado en Tecnologías de la Información y las ComunicacionesEsta tesis doctoral se presenta bajo la modalidad de compendio de publicaciones. Está formada por un total de cuatro artículos. Article 1.-: A. Gil-Martinez, M. Poveda-Garcia, J. A. Lopez-Pastor, J. C. Sanchez-Aarnoutse and J. L. Gomez-Tornero, Wi-Fi Direction Finding with Frequency-Scanned Antenna and Channel Hopping Scheme IEEE sensors Journal, , vol. 22, no. 6, pp. 5210-5222, 2022. DOI: 10.1109/JSEN.2021.3122232. Article 2.-: A. Gil-Martinez, M. Poveda-Garcia, D. Cañete-Rebenaque, and J. L. Gomez-Tornero, Frequency-Scanned Monopulse Antenna for RSSI-based Direction Finding of UHF RFID tags IEEE Antennas and Wireless Propagation Letters,, vol. 21, no. 1, pp. 158-162, 2022. DOI: 10.1109/LAWP.2021.3122232. Article 3.-: A. Gil-Martinez, M. Poveda-Garcia, J. Garcia-Fernandez, M. Campo-Valera, D. Cañete-Rebenaque, and J. L. Gomez-Tornero, Direction Finding of RFID tags in UHF Band Using a Passive Beam-Scanning Leaky-Wave Antenna IEEE Journal of Radio Frequency Identi cation, doi: 10.1109/JRFID.2021.3122233. Article 4.-: J. L. Gomez-Tornero, A. Gil-Martinez, M. Poveda-Garcia and D. Cañete-Rebenaque, ARIEL: Passive Beam-Scanning Antenna TeRminal for Iridiscent and E cient LEO Satellite Connectivity in IEEE Antennas and Wireless Propagation Letters, doi: 10.1109/LAWP.2022.3193040.Universidad Politécnica de Cartagen
- …
