CAVERDOCK: A new tool for analysis of ligand binding and unbinding based on molecular docking

Understanding the protein-ligand interactions is crucial for engineering improved catalysts. The interaction of a protein and a ligand molecule often takes place in enzymes active site. Such functional sites may be buried inside the protein core, and therefore a transport of a ligand from outside environment to the protein inside needs to be understood. Here we present the CaverDock [1], implementing a novel method for analysis of these important transport processes. Our method is based on a modified molecular docking algorithm. It iteratively places the ligand along the tunnel in such a way that the ligand movement is contiguous and its energy is minimized. The output of the calculation is ligand trajectory and energy profile of transport process. CaverDock uses a modified version of the program AutoDock Vina [2] for molecular docking and implements a parallel heuristic algorithm to search the space of possible trajectories. Our method lies in between of geometrical approaches and molecular dynamics simulations. Contrary to geometrical methods, it provides an evaluation of chemical forces. However, it is not as computationally demanding as the methods based on molecular dynamics. The typical input of CaverDock requires setup for molecular docking and tunnel geometry obtained from Caver [3]. Typical computational time is in dozens of minutes at a single node, allowing virtual screening of a large pool of molecules. We demonstrate CaverDock usability by comparison of a ligand trajectory in different tunnels of wild type and engineered proteins; and computation of energetic profiles for a large set of substrates and inhibitors. CaverDock is available from the web site http://www.caver.cz. 1. Vavra, O., Filipovic, J., Plhak, J., Bednar, D., Marques, S., Brezovsky, J., Matyska, L., Damborsky, J., CAVERDOCK: A New Tool for Analysis of Ligand Binding and Unbinding Based on Molecular Docking. PLOS Computational Biology (submitted). 2. Trott, O., Olson, A.J., AutoDock Vina: Improving the Speed and Accuracy of Docking with a New scoring function, efficient optimization and multithreading, Journal of Computational Chemistry 31: 455-461, 2010. 3. Chovancova, E., Pavelka, A., Benes, P., Strnad, O., Brezovsky, J., Kozlikova, B., Gora, A., Sustr, V., Klvana, M., Medek, P., Biedermannova, L., Sochor, J., Damborsky, J., 2012: CAVER 3.0: A Tool for Analysis of Transport Pathways in Dynamic Protein Structures. PLOS Computational Biology 8: e1002708

Common ELIXIR Service for Researcher Authentication and Authorisation

Linden M, Prochazka M, Lappalainen I, et al. Common ELIXIR Service for Researcher Authentication and Authorisation. F1000Research. 2018;7: 1199.A common Authentication and Authorisation Infrastructure (AAI) that would allow single sign-on to services has been identified as a key enabler for European bioinformatics. ELIXIR AAI is an ELIXIR service portfolio for authenticating researchers to ELIXIR services and assisting these services on user privileges during research usage. It relieves the scientific service providers from managing the user identities and authorisation themselves, enables the researcher to have a single set of credentials to all ELIXIR services and supports meeting the requirements imposed by the data protection laws. ELIXIR AAI was launched in late 2016 and is part of the ELIXIR Compute platform portfolio. By the end of 2017 the number of users reached 1000, while the number of relying scientific services was 36. This paper presents the requirements and design of the ELIXIR AAI and the policies related to its use, and how it can be used for serving some example services, such as document management, social media, data discovery, human data access, cloud compute and training services

Federated Identity Management for Research Collaborations

This white-paper expresses common requirements of Research Communities seeking to leverage Identity Federation for Authentication and Authorisation. Recommendations are made to Stakeholders to guide the future evolution of Federated Identity Management in a direction that better satisfies research use cases. The authors represent research communities, Research Services, Infrastructures, Identity Federations and Interfederations, with a joint motivation to ease collaboration for distributed researchers. The content has been edited collaboratively by the Federated Identity Management for Research (FIM4R) Community, with input sought at conferences and meetings in Europe, Asia and North America

INDIGO-DataCloud: A data and computing platform to facilitate seamless access to e-infrastructures

This paper describes the achievements of the H2020 project INDIGO-DataCloud. The project has provided e-infrastructures with tools, applications and cloud framework enhancements to manage the demanding requirements of scientific communities, either locally or through enhanced interfaces. The middleware developed allows to federate hybrid resources, to easily write, port and run scientific applications to the cloud. In particular, we have extended existing PaaS (Platform as a Service) solutions, allowing public and private e-infrastructures, including those provided by EGI, EUDAT, and Helix Nebula, to integrate their existing services and make them available through AAI services compliant with GEANT interfederation policies, thus guaranteeing transparency and trust in the provisioning of such services. Our middleware facilitates the execution of applications using containers on Cloud and Grid based infrastructures, as well as on HPC clusters. Our developments are freely downloadable as open source components, and are already being integrated into many scientific applications

Mobile computing

Notebooks are replacing other personal computers in everyday use. Efficient use of such mobile devices requires a creation of an "illusion" of permanent high speed on-line connection. Infrastructure support including middle-ware services is necessary for such environment. E-mail, (distributed) filesystems or computational experiment steering are examples of services which utility is qualitatively increased by such a support. A model of middle-ware support that is based on tunneling and caching is presented. It is also shown how the requirements for mobile computing support are in many aspects analogous to those needed to build large scale GRID systems. Information systems, services discovery, and security issues are discussed

Active networks and high speed content delivery

Future computer networks must be more flexible and faster then today. Active network paradigm is the way how to add flexibility to networks. During the last five years, a number of models for active networks realization were presented. In active networks, the concept of network as a distributed programmed facility is developed. This concept makes possible new applications and special services. Active network models are described and our active network model is described in more detail. We discus applications which need special network features and the position active routers and switches have in network infrastructure in order to satisfy these demands. An application which supports collaborative work, requiring data, audio and video streams to be transferred through the network is used to demonstrate how active network element can process dataflows with specific features in both uni- and multicast environments. An overly of active network elements placed in particular points of the non-intelligent high speed network is presented as a model which supports both the intelligence and high throughput without need of specialized costly hardware support