MD-DATA: the legacy of the ABC Consortium

The ABC Consortium has been generating nucleic-acids MD trajectories for more than 20 years. This brief comment highlights the importance of this data for the field, which triggered a number of critical studies, including force-field parameterization and development of new coarse-grained and mesoscopic models. With the world entering into a new data-driven era led by artificial intelligence, where data is becoming more essential than ever, the ABC initiative is leading the way for nucleic acid flexibility

The multiple roles of waters in protein solvation

Extensive molecular dynamics (MD) simulations have been used to characterize the multiple roles of water in solvating different types of proteins under different environmental conditions. We analyzed a small set of proteins, representative of the most prevalent meta-folds under native conditions, in the presence of crowding agents, and at high temperature with or without high concentration of urea. We considered also a protein in the unfolded state as characterized by NMR and atomistic MD simulations. Our results outline the main characteristics of the hydration environment of proteins and illustrate the dramatic plasticity of water, and its chameleonic ability to stabilize proteins under a variety of conditions

A numerical study into the evolution of loads on shores and slabs during construction of multistorey buildings. Comparison of partial striking with other techniques

This paper contains a summary and evaluation of an experimental research project carried out at the ICITECH laboratories, Valencia, Spain. The project consisted of the construction of a full-scale building that included a process of shoring, clearing and striking (SCS). The experimental model was used as the basis for the development of a FE model, including an evolving calculation, with the objective of simulating the construction process used, as well as studying the evolution of concrete properties during the test. The FE model was verified with the results obtained from the experimental model. Two further FE models were then developed from the original model and used to simulate the construction of the same building using two different construction processes: one involving shoring and striking (SS) and the other shoring, re-shoring and striking (SRS). Finally, the SCS was compared to the SS and SRS processes, respectively, and an analysis was made of the advantages and disadvantages of each one. The paper breaks new ground in that for the first time ever a comparative study is made of the three most frequently used shoring techniques. (C) 2010 Elsevier Ltd. All rights reserved.The authors would like express their gratitude to the Spanish Ministry for Science and Technology for funding the project (BIA2004-02085) and also to the Encofrados J. Alsina, Copasa, Lafarge and Ros Casares companies for their invaluable cooperation.Alvarado Vargas, YA.; Calderón García, PA.; Gasch, I.; Adam Martínez, JM. (2010). A numerical study into the evolution of loads on shores and slabs during construction of multistorey buildings. Comparison of partial striking with other techniques. Engineering Structures. 32(10):3093-3102. doi:10.1016/j.engstruct.2010.05.028S30933102321

BioExcel Building Blocks Workflows (BioBB-Wfs), an integrated web-based plartform for biomolecular simulations.

We present BioExcel Building Blocks Workflows, a web-based graphical user interface (GUI) offering access to a collection of transversal pre-configured biomolecular simulation workflows assembled with the BioExcel Building Blocks library. Available workflows include Molecular Dynamics setup, protein-ligand docking, trajectory analyses and small molecule parameterization. Workflows can be launched in the platform or downloaded to be run in the users' own premises. Remote launching of long executions to user's available High-Performance computers is possible, only requiring configuration of the appropriate access credentials. The web-based graphical user interface offers a high level of interactivity, with integration with the NGL viewer to visualize and check 3D structures, MDsrv to visualize trajectories, and Plotly to explore 2D plots. The server requires no login but is recommended to store the users' projects and manage sensitive information such as remote credentials. Private projects can be made public and shared with colleagues with a simple URL. The tool will help biomolecular simulation users with the most common and repetitive processes by means of a very intuitive and interactive graphical user interface. The server is accessible at https://mmb.irbbarcelona.org/biobb-wfs

Bioactive conformational ensemble server and database. A public framework to speed up in silico drug discovery.

Modern high-throughput structure-based drug discovery algorithms consider ligand flexibility, but typically with low accuracy, which results in a loss of performance in the derived models. Here we present the Bioactive Conformational Ensemble (BCE) server and its associated database. The server creates conformational ensembles of drug-like ligands and stores them in the BCE database, where a variety of analyses are offered to the user. The workflow implemented in the BCE server combines enhanced sampling molecular dynamics with self-consistent reaction field quantum mechanics (SCRF/QM) calculations. The server automatizes all the steps to transform 1D or 2D representation of drugs into three dimensional molecules, which are then titrated, parametrized, hydrated and optimized before being subjected to Hamiltonian replica-exchange (HREX) molecular dynamics simulations. Ensembles are collected and subjected to a clustering procedure to derive representative conformers, which are then analyzed at the SCRF/QM level of theory. All structural data is organized in a noSQL database accessible through a graphical interface and in a programmatic manner through a REST API. The server allows the user to define a private workspace and offers a deposition protocol as well as input files for "in house" calculations in those cases where confidentiality is a must. The database and the associated server are available at https://mmb.irbbarcelona.org/BC

Improving construction processes of concrete building structures using load limiters on shores

This paper analyses the redistribution of maximum loads using a system of load limiters on shores in which the limiters yield at a given load and thus reduce the maximum load absorbed by the shores. For this analysis a finite element modelling (FEM) of an experimental building was developed in which load limiters had been fitted to the shores to restrict their maximum load to a given value. This was designed to: (a) optimise slab construction costs by using shores of lower load-bearing capacities, (b) improve safety during the construction of consecutive concrete slab floors by reducing maximum loads and redistributing loads amongst the shores; and (c) increase structural efficiency by more efficient use of the materials employed due to load redistribution. It has been estimated that using load limiters in this way can reduce total shoring costs in a building project by between 30% and 40%.The authors would like to express their gratitude to the Universitat Politecnica de Valencia for funding this research project (PAID-06-11) and also to the Encofrados J. Alsina Company for their invaluable cooperation.Buitrago Moreno, M.; Alvarado Vargas, YA.; Adam Martínez, JM.; Calderón García, PA.; Gasch, I.; Moragues, JJ. (2015). Improving construction processes of concrete building structures using load limiters on shores. Engineering Structures. 100:104-115. doi:10.1016/j.engstruct.2015.06.007S10411510

DNA structure directs positioning of the mitochondrial genome packaging protein Abf2p.

The mitochondrial genome (mtDNA) is assembled into nucleo-protein structures termed nucleoids and maintained differently compared to nuclear DNA, the involved molecular basis remaining poorly understood. In yeast (Saccharomyces cerevisiae), mtDNA is a ∼80 kbp linear molecule and Abf2p, a double HMG-box protein, packages and maintains it. The protein binds DNA in a non-sequence-specific manner, but displays a distinct 'phased-binding' at specific DNA sequences containing poly-adenine tracts (A-tracts). We present here two crystal structures of Abf2p in complex with mtDNA-derived fragments bearing A-tracts. Each HMG-box of Abf2p induces a 90° bend in the contacted DNA, causing an overall U-turn. Together with previous data, this suggests that U-turn formation is the universal mechanism underlying mtDNA compaction induced by HMG-box proteins. Combining this structural information with mutational, biophysical and computational analyses, we reveal a unique DNA binding mechanism for Abf2p where a characteristic N-terminal flag and helix are crucial for mtDNA maintenance. Additionally, we provide the molecular basis for A-tract mediated exclusion of Abf2p binding. Due to high prevalence of A-tracts in yeast mtDNA, this has critical relevance for nucleoid architecture. Therefore, an unprecedented A-tract mediated protein positioning mechanism regulates DNA packaging proteins in the mitochondria, and in combination with DNA-bending and U-turn formation, governs mtDNA compaction

The BioExcel methodology for developing dynamic, scalable, reliable and portable computational biomolecular workflows

Developing complex biomolecular workflows is not always straightforward. It requires tedious developments to enable the interoperability between the different biomolecular simulation and analysis tools. Moreover, the need to execute the pipelines on distributed systems increases the complexity of these developments. To address these issues, we propose a methodology to simplify the implementation of these workflows on HPC infrastructures. It combines a library, the BioExcel Building Blocks (BioBBs), that allows scientists to implement biomolecular pipelines as Python scripts, and the PyCOMPSs programming framework which allows to easily convert Python scripts into task-based parallel workflows executed in distributed computing systems such as HPC clusters, clouds, containerized platforms, etc. Using this methodology, we have implemented a set of computational molecular workflows and we have performed several experiments to validate its portability, scalability, reliability and malleability.This work has been supported by Spanish Ministry of Science and Innovation MCIN/AEI/10.13039/501100011033 under contract PID2019-107255GB-C21, by the Generalitat de Catalunya under contracts 2017-SGR-01414 and 2017-SGR1110, by the European Commission through the BioExcel Center of Excellence (Horizon 2020 Framework program) under contracts 823830, and 675728. This work is also partially supported by the CECH project which has been co-funded with 50% by the European Regional Development Fund under the framework of the ERFD Operative Programme for Catalunya 2014-2020, with a grant of 1.527.637,88€.Peer ReviewedPostprint (author's final draft

Woven Thermal Protection System (WTPS) a Novel Approach to Meet Nasa's Most Demanding Reentry Missions

NASA's future robotic missions to Venus and other planets, namely, Saturn, Uranus, Neptune, result in extremely high entry conditions that exceed the capabilities of current mid density ablators (PICA or Avcoat). Therefore mission planners assume the use of a fully dense carbon phenolic heatshield similar to what was flown on Pioneer Venus and Galileo. Carbon phenolic is a robust TPS, however, its high density and thermal conductivity constrain mission planners to steep entries, high fluxes, pressures and short entry durations, in order for CP to be feasible from a mass perspective. The high entry conditions pose certification challenges in existing ground based test facilities. In 2012 the Game Changing Development Program in NASA's Space Technology Mission Directorate funded NASA ARC to investigate the feasibility of a Woven Thermal Protection System to meet the needs of NASA's most challenging entry missions. This presentation will summarize the maturation of the WTPS project

Experimentally induced incomplete burst fractures - a novel technique for calf and human specimens

Background: Fracture morphology is crucial for the clinical decision-making process preceding spinal fracture treatment. The presented experimental approach was designed in order to ensure reproducibility of induced fracture morphology. Results: The presented method resulted in fracture morphology, found in clinical classification systems like the Magerl classification. In the calf spine samples, 70% displayed incomplete burst fractures corresponding to type A3.1 and A3.2 fractures. In all human samples, superior incomplete burst fractures (Magerl A3.1) were identified by an independent radiologist and spine surgeon. Conclusions: The presented set up enables the first experimental means to reliably model and study distinct incomplete burst fracture patterns in an in vitro setting. Thus, we envisage this protocol to facilitate further studies on spine fracture treatment of incomplete burst fractures