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Exascale computing has been a dream for ages and is close to becoming a reality that will impact how molecular simulations are being performed, as well as the quantity and quality of the information derived for them. We review how the biomolecular simulations field is anticipating these new architectures, making emphasis on recent work from groups in the BioExcel Center of Excellence for High Performance Computing. We exemplified the power of these simulation strategies with the work done by the HPC simulation community to fight Covid-19 pandemics.

We present Nucleosome Dynamics, a suite of programs integrated into a virtual research environment and created to define nucleosome architecture and dynamics from noisy experimental data. The package allows both the definition of nucleosome architectures and the detection of changes in nucleosomal organization due to changes in cellular conditions. Results are displayed in the context of genomic information thanks to different visualizers and browsers, allowing the user a holistic, multidimensional view of the genome/transcriptome. The package shows good performance for both locating equilibrium nucleosome architecture and nucleosome dynamics and provides abundant useful information in several test cases, where experimental data on nucleosome position (and for some cases expression level) have been collected for cells under different external conditions (cell cycle phase, yeast metabolic cycle progression, changes in nutrients or difference in MNase digestion level). Nucleosome Dynamics is a free software and is provided under several distribution models., M.O. is an ICREA (Institució Catalana de Recerca i Estudis Avancats) academia researcher; Spanish Ministry of Science [RTI2018-096704-B-100]; Catalan Government [2017-SGR-134]; Instituto de Salud Carlos III–Instituto Nacional de Bioinformática, the European Union's Horizon 2020 research and innovation program, and the Biomolecular and Bioinformatics Resources Platform [ISCIII PT 17/0009/0007 co-funded by the Fondo Europeo de Desarrollo Regional FEDER; Grants Elixir-Excelerate: 676559 and BioExcel2: 823830; ERC:812850; MuG-676566]; MINECO Severo Ochoa Award of Excellence from the Government of Spain (awarded to IRB Barcelona). Funding for open access charge: Spanish Ministry of Science [RTI2018-096704-B-100]., Peer Reviewed, Postprint (published version)

Interoperable metadata is key for the management of genomic information. We propose a flexible approach that we contribute to the standardization by ISO/IEC of a new format for efficient and secure compressed storage and transmission of genomic information., Peer Reviewed, Postprint (published version)

Interoperable metadata is key for the management of genomic information. We propose a flexible approach that we contribute to the standardization by ISO/IEC of a new format for efficient and secure compressed storage and transmission of genomic information, This work is partly supported by the Spanish Government (GenCom, TEC2015-67774- C2-1-R and TEC2015-67774-2-R). We also thank the EGA team for their valuable comments., Peer Reviewed, Postprint (author's final draft)

The dependence of life scientists on software has steadily grown in recent years. For many tasks, researchers have to decide which of the available bioinformatics software are more suitable for their specific needs. Additionally researchers should be able to objectively select the software that provides the highest accuracy, the best efficiency and the highest level of reproducibility when integrated in their research projects. Critical benchmarking of bioinformatics methods, tools and web services is therefore an essential community service, as well as a critical component of reproducibility efforts. Unbiased and objective evaluations are challenging to set up and can only be effective when built and implemented around community driven efforts, as demonstrated by the many ongoing community challenges in bioinformatics that followed the success of CASP. Community challenges bring the combined benefits of intense collaboration, transparency and standard harmonization. Only open systems for the continuous evaluation of methods offer a perfect complement to community challenges, offering to larger communities of users that could extend far beyond the community of developers, a window to the developments status that they can use for their specific projects. We understand by continuous evaluation systems as those services which are always available and periodically update their data and/or metrics according to a predefined schedule keeping in mind that the performance has to be always seen in terms of each research domain. We argue here that technology is now mature to bring community driven benchmarking efforts to a higher level that should allow effective interoperability of benchmarks across related methods. New technological developments allow overcoming the limitations of the first experiences on online benchmarking e.g. EVA. We therefore describe OpenEBench, a novel infra-structure designed to establish a continuous automated benchmarking system for bioinformatics, Preprint

We present here a full update of the PMut predictor, active since 2005 and with a large acceptance in the field of predicting Mendelian pathological mutations. PMut internal engine has been renewed, and converted into a fully featured standalone training and prediction engine that not only powers PMut web portal, but that can generate custom predictors with alternative training sets or validation schemas. PMut Web portal allows the user to perform pathology predictions, to access a complete repository of pre-calculated predictions, and to generate and validate new predictors. The default predictor performs with good quality scores (MCC values of 0.61 on 10-fold cross validation, and 0.42 on a blind test with SwissVar 2016 mutations). The PMut portal is freely accessible at http://mmb.irbbarcelona.org/PMut. A complete help and tutorial is available at http://mmb.irbbarcelona.org/PMut/help., Spanish Ministry of Science [BIO2015-64802-R-32868, SEV-2015-0493, TIN2012-34557, TEC2015-67774-C2-2-R, SAF2016-80255-R]; Catalan Government [2014-SGR-134, 2014-SGR-1051]; Instituto de Salud Carlos III-Instituto Nacional de Bioinformática [INB; PT13/0001/0019, PT13/0001/0028]; European Union, H2020 programme [Elixir-Excelerate: 676559; BioExcel: 674728 and MuG: 676566]; La Caixa Foundation fellowship [to V.L.F.]. Funding for open access charge: European Union and Spanish Ministry of Science., Peer Reviewed, Postprint (published version)

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., The authors thank INB (Instituto Nacional de Bioinformática) for support in this project. Additional funding to this project comes from H2020 (BioExcel GA 675728, Elixir-Excelerate GA 676559) and the Spanish MINECO (BIO2015/64802-R) funding agencies. IRB Barcelona is recipient of a Severo Ochoa Award of Excellence from MINECO (Government of Spain, GA SEV-2015-050). MO is an ICREA Academia researcher., Peer Reviewed, Postprint (author's final draft)

We present a systematic study of the long-timescale dynamics of the Drew–Dickerson dodecamer (DDD: d(CGCGAATTGCGC)2) a prototypical B-DNA duplex. Using our newly parameterized PARMBSC1 force field, we describe the conformational landscape of DDD in a variety of ionic environments from minimal salt to 2 M Na+Cl− or K+Cl−. The sensitivity of the simulations to the use of different solvent and ion models is analyzed in detail using multi-microsecond simulations. Finally, an extended (10 μs) simulation is used to characterize slow and infrequent conformational changes in DDD, leading to the identification of previously uncharacterized conformational states of this duplex which can explain biologically relevant conformational transitions. With a total of more than 43 μs of unrestrained molecular dynamics simulation, this study is the most extensive investigation of the dynamics of the most prototypical DNA duplex., MINECO Severo Ochoa Award of Excellence (Government of Spain) (to IRB Barcelona); Spanish Ministry of Science [BIO2012-32868, BFU2014-61670-EXP to M.O.]; Catalan SGR (to M.O.); Instituto Nacional de Bioinformática (to M.O.); European Research Council (ERC SimDNA) (to M.O.); H2020 program (MuG and BioExcel projects) (to M.O.); Czech Republic Grant Agency [14-21893S to T.D., F.L.]; ANR grant CHROME [ANR-12-BSV5-0017-01 to R.L.]. Funding for open access charge: European Research Council (ERC SimDNA)., Peer Reviewed, Award-winning, Postprint (author's final draft)

Molecular dynamics simulation (MD) is, just behind genomics, the bioinformatics tool that generates the largest amounts of data, and that is using the largest amount of CPU time in supercomputing centres. MD trajectories are obtained after months of calculations, analysed in situ, and in practice forgotten. Several projects to generate stable trajectory databases have been developed for proteins, but no equivalence exists in the nucleic acids world. We present here a novel database system to store MD trajectories and analyses of nucleic acids. The initial data set available consists mainly of the benchmark of the new molecular dynamics force-field, parmBSC1. It contains 156 simulations, with over 120 of total simulation time. A deposition protocol is available to accept the submission of new trajectory data. The database is based on the combination of two NoSQL engines, Cassandra for storing trajectories and MongoDB to store analysis results and simulation metadata. The analyses available include backbone geometries, helical analysis, NMR observables and a variety of mechanical analyses. Individual trajectories and combined meta-trajectories can be downloaded from the portal. The system is accessible through http: //mmb.irbbarcelona.org/BIGNASim/. Supplementary Material is also available on-line at http://mmb. irbbarcelona.org/BIGNASim/SuppMaterial/., Spanish Ministry of Science [BIO2012-32868, SEV-2011-00067, TIN2012-34557]; Catalan Government [2014-SGR-134, 2014-SGR-1051]; Institut Català de Recerca I Estudis Avanc¸ats, ICREA Academia [to M.O.], Instituto de Salud Carlos III-Instituto Nacional de Bioinformática [PT13/0001/0019, PT13/0001/0028]; European Research Council [ERC SimDNA]; European Union, H2020 programme [Elixir-Excellerate: 676559; BioExcel: 674728, MuG: 676566]; PEDECIBA and SNI (ANII, Uruguay) [to P.D.D.]. Funding for open access charge: European Union [MuG: 676566]., Peer Reviewed, Postprint (published version)

Molecular dynamics simulation (MD) is, just behind genomics, the bioinformatics tool that generates the largest amounts of data, and that is using the largest amount of CPU time in supercomputing centres. MD trajectories are obtained after months of calculations, analysed in situ, and in practice forgotten. Several projects to generate stable trajectory databases have been developed for proteins, but no equivalence exists in the nucleic acids world. We present here a novel database system to store MD trajectories and analyses of nucleic acids. The initial data set available consists mainly of the benchmark of the new molecular dynamics force-field, parmBSC1. It contains 156 simulations, with over 120 mu s of total simulation time. A deposition protocol is available to accept the submission of new trajectory data. The database is based on the combination of two NoSQL engines, Cassandra for storing trajectories and MongoDB to store analysis results and simulation metadata. The analyses available include backbone geometries, helical analysis, NMR observables and a variety of mechanical analyses. Individual trajectories and combined meta-trajectories can be downloaded from the portal. The system is accessible through http://mmb.irbbarcelona.org/BIGNASim/. Supplementary Material is also available on-line at http://mmb.irbbarcelona.org/BIGNASim/SuppMaterial/., Peer Reviewed, Postprint (published version)

We present parmbsc1, a force field for DNA atomistic simulation, which has been parameterized from high-level quantum mechanical data and tested for nearly 100 systems (representing a total simulation time of ~140 μs) covering most of DNA structural space. Parmbsc1 provides high-quality results in diverse systems. Parameters and trajectories are available at http://mmb.irbbarcelona.org/ParmBSC1/., MO thanks Spanish Ministry of Science (BIO2012-32868), the Catalan SGR, the Instituto Nacional de Bioinformática, and the European Research Council (ERC_SimDNA) for support. MO is an ICREA academia researcher. MO thanks CPU/GPU time on MareNostrum/MinoTauro (BSC). CAL, SAH and AN thanks the UK HECBioSim Consortium for HPC time on ARCHER (Grant EP/L000253/1). AN was supported by the Biotechnology and Biological Sciences Research Council (BBSRC, grant number BB/I019294/1), and thanks ARC Leeds for computational resources. PDD is a PEDECIBA and SNI (ANII, Uruguay) researcher. DAC thanks Chunmei Liu for assistance with the crystal simulation analysis., Peer Reviewed, Postprint (author's final draft)