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      MitImpact 3: modeling the residue interaction network of the Respiratory Chain subunits

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          Abstract

          Numerous lines of evidence have shown that the interaction between the nuclear and mitochondrial genomes ensures the efficient functioning of the OXPHOS complexes, with substantial implications in bioenergetics, adaptation, and disease. Their interaction is a fascinating and complex trait of the eukaryotic cell that MitImpact explores with its third major release. MitImpact expands its collection of genomic, clinical, and functional annotations of all non-synonymous substitutions of the human mitochondrial genome with new information on putative Compensated Pathogenic Deviations and co-varying amino acid sites of the Respiratory Chain subunits. It further provides evidence of energetic and structural residue compensation by techniques of molecular dynamics simulation. MitImpact is freely accessible at http://mitimpact.css-mendel.it.

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          UCSF Chimera--a visualization system for exploratory research and analysis.

          The design, implementation, and capabilities of an extensible visualization system, UCSF Chimera, are discussed. Chimera is segmented into a core that provides basic services and visualization, and extensions that provide most higher level functionality. This architecture ensures that the extension mechanism satisfies the demands of outside developers who wish to incorporate new features. Two unusual extensions are presented: Multiscale, which adds the ability to visualize large-scale molecular assemblies such as viral coats, and Collaboratory, which allows researchers to share a Chimera session interactively despite being at separate locales. Other extensions include Multalign Viewer, for showing multiple sequence alignments and associated structures; ViewDock, for screening docked ligand orientations; Movie, for replaying molecular dynamics trajectories; and Volume Viewer, for display and analysis of volumetric data. A discussion of the usage of Chimera in real-world situations is given, along with anticipated future directions. Chimera includes full user documentation, is free to academic and nonprofit users, and is available for Microsoft Windows, Linux, Apple Mac OS X, SGI IRIX, and HP Tru64 Unix from http://www.cgl.ucsf.edu/chimera/. Copyright 2004 Wiley Periodicals, Inc.
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            SWISS-MODEL: homology modelling of protein structures and complexes

            Abstract Homology modelling has matured into an important technique in structural biology, significantly contributing to narrowing the gap between known protein sequences and experimentally determined structures. Fully automated workflows and servers simplify and streamline the homology modelling process, also allowing users without a specific computational expertise to generate reliable protein models and have easy access to modelling results, their visualization and interpretation. Here, we present an update to the SWISS-MODEL server, which pioneered the field of automated modelling 25 years ago and been continuously further developed. Recently, its functionality has been extended to the modelling of homo- and heteromeric complexes. Starting from the amino acid sequences of the interacting proteins, both the stoichiometry and the overall structure of the complex are inferred by homology modelling. Other major improvements include the implementation of a new modelling engine, ProMod3 and the introduction a new local model quality estimation method, QMEANDisCo. SWISS-MODEL is freely available at https://swissmodel.expasy.org.
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              ClinVar: improving access to variant interpretations and supporting evidence

              Abstract ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/) is a freely available, public archive of human genetic variants and interpretations of their significance to disease, maintained at the National Institutes of Health. Interpretations of the clinical significance of variants are submitted by clinical testing laboratories, research laboratories, expert panels and other groups. ClinVar aggregates data by variant-disease pairs, and by variant (or set of variants). Data aggregated by variant are accessible on the website, in an improved set of variant call format files and as a new comprehensive XML report. ClinVar recently started accepting submissions that are focused primarily on providing phenotypic information for individuals who have had genetic testing. Submissions may come from clinical providers providing their own interpretation of the variant (‘provider interpretation’) or from groups such as patient registries that primarily provide phenotypic information from patients (‘phenotyping only’). ClinVar continues to make improvements to its search and retrieval functions. Several new fields are now indexed for more precise searching, and filters allow the user to narrow down a large set of search results.
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                Author and article information

                Contributors
                Journal
                Nucleic Acids Res
                Nucleic Acids Res
                nar
                Nucleic Acids Research
                Oxford University Press
                0305-1048
                1362-4962
                08 January 2021
                09 December 2020
                09 December 2020
                : 49
                : D1
                : D1282-D1288
                Affiliations
                Laboratory of Bioinformatics, IRCCS Casa Sollievo della Sofferenza , San Giovanni Rotondo (FG), 71013, Italy
                Laboratory of Bioinformatics, IRCCS Casa Sollievo della Sofferenza , San Giovanni Rotondo (FG), 71013, Italy
                Laboratory of Bioinformatics, IRCCS Casa Sollievo della Sofferenza , San Giovanni Rotondo (FG), 71013, Italy
                Department of Experimental Medicine, Sapienza University of Rome , Rome 00161, Italy
                Laboratory of Bioinformatics, IRCCS Casa Sollievo della Sofferenza , San Giovanni Rotondo (FG), 71013, Italy
                Department of Experimental Medicine, Sapienza University of Rome , Rome 00161, Italy
                Department of Experimental Medicine, Sapienza University of Rome , Rome 00161, Italy
                ISBReMIT Institute for Stem Cell Biology, Regenerative Medicine and Innovative Therapies, IRCSS Casa Sollievo della Sofferenza , San Giovanni Rotondo (FG), 71013, Italy
                Laboratory of Medical Genetics, IRCCS Casa Sollievo della Sofferenza , San Giovanni Rotondo (FG) 71013, Italy
                Laboratory of Bioinformatics, IRCCS Casa Sollievo della Sofferenza , San Giovanni Rotondo (FG), 71013, Italy
                Author notes
                To whom correspondence should be addressed. Tel: +39 06 44160526; Fax: +39 06 44160548; Email: t.mazza@ 123456css-mendel.it
                Author information
                http://orcid.org/0000-0003-0434-8533
                Article
                gkaa1032
                10.1093/nar/gkaa1032
                7779045
                33300029
                6dbc3a77-0658-4b8c-8fdf-8940e640116e
                © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 08 December 2020
                : 14 October 2020
                : 08 August 2020
                Page count
                Pages: 7
                Funding
                Funded by: Italian Ministry of Health;
                Categories
                AcademicSubjects/SCI00010
                Database Issue

                Genetics
                Genetics

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