MetalS²: A Tool for the Structural Alignment of Minimal Functional Sites in Metal-Binding Proteins and Nucleic Acids

We developed a new software tool, MetalS2, for the structural alignment of Minimal Functional Sites (MFSs) in metal-binding biological macromolecules. MFSs are 3D templates that describe the local environment around the metal(s) independently of the larger context of the macromolecular structure. Such local environment has a determinant role in tuning the chemical reactivity of the metal, ultimately contributing to the functional properties of the whole system. On our example data sets, MetalS2 unveiled structural similarities that other programs for protein structure comparison do not consistently point out and overall identified a larger number of structurally similar MFSs. MetalS2 supports the comparison of MFSs harboring different metals and/or with different nuclearity and is available both as a stand-alone program and a Web tool (http://metalweb.cerm.unifi.it/tools/metals2/)

MetalS²: A Tool for the Structural Alignment of Minimal Functional Sites in Metal-Binding Proteins and Nucleic Acids

We developed a new software tool, MetalS², for the structural alignment of Minimal Functional Sites (MFSs) in metal-binding biological macromolecules. MFSs are 3D templates that describe the local environment around the metal(s) independently of the larger context of the macromolecular structure. Such local environment has a determinant role in tuning the chemical reactivity of the metal, ultimately contributing to the functional properties of the whole system. On our example data sets, MetalS² unveiled structural similarities that other programs for protein structure comparison do not consistently point out and overall identified a larger number of structurally similar MFSs. MetalS² supports the comparison of MFSs harboring different metals and/or with different nuclearity and is available both as a stand-alone program and a Web tool (http://metalweb.cerm.unifi.it/tools/metals2/)

MetalS²: A Tool for the Structural Alignment of Minimal Functional Sites in Metal-Binding Proteins and Nucleic Acids

We developed a new software tool, MetalS², for the structural alignment of Minimal Functional Sites (MFSs) in metal-binding biological macromolecules. MFSs are 3D templates that describe the local environment around the metal(s) independently of the larger context of the macromolecular structure. Such local environment has a determinant role in tuning the chemical reactivity of the metal, ultimately contributing to the functional properties of the whole system. On our example data sets, MetalS² unveiled structural similarities that other programs for protein structure comparison do not consistently point out and overall identified a larger number of structurally similar MFSs. MetalS² supports the comparison of MFSs harboring different metals and/or with different nuclearity and is available both as a stand-alone program and a Web tool (http://metalweb.cerm.unifi.it/tools/metals2/)

MetalS²: A Tool for the Structural Alignment of Minimal Functional Sites in Metal-Binding Proteins and Nucleic Acids

We developed a new software tool, MetalS², for the structural alignment of Minimal Functional Sites (MFSs) in metal-binding biological macromolecules. MFSs are 3D templates that describe the local environment around the metal(s) independently of the larger context of the macromolecular structure. Such local environment has a determinant role in tuning the chemical reactivity of the metal, ultimately contributing to the functional properties of the whole system. On our example data sets, MetalS² unveiled structural similarities that other programs for protein structure comparison do not consistently point out and overall identified a larger number of structurally similar MFSs. MetalS² supports the comparison of MFSs harboring different metals and/or with different nuclearity and is available both as a stand-alone program and a Web tool (http://metalweb.cerm.unifi.it/tools/metals2/)

MetalS²: A Tool for the Structural Alignment of Minimal Functional Sites in Metal-Binding Proteins and Nucleic Acids

We developed a new software tool, MetalS², for the structural alignment of Minimal Functional Sites (MFSs) in metal-binding biological macromolecules. MFSs are 3D templates that describe the local environment around the metal(s) independently of the larger context of the macromolecular structure. Such local environment has a determinant role in tuning the chemical reactivity of the metal, ultimately contributing to the functional properties of the whole system. On our example data sets, MetalS² unveiled structural similarities that other programs for protein structure comparison do not consistently point out and overall identified a larger number of structurally similar MFSs. MetalS² supports the comparison of MFSs harboring different metals and/or with different nuclearity and is available both as a stand-alone program and a Web tool (http://metalweb.cerm.unifi.it/tools/metals2/)

MetalS²: A Tool for the Structural Alignment of Minimal Functional Sites in Metal-Binding Proteins and Nucleic Acids

We developed a new software tool, MetalS², for the structural alignment of Minimal Functional Sites (MFSs) in metal-binding biological macromolecules. MFSs are 3D templates that describe the local environment around the metal(s) independently of the larger context of the macromolecular structure. Such local environment has a determinant role in tuning the chemical reactivity of the metal, ultimately contributing to the functional properties of the whole system. On our example data sets, MetalS² unveiled structural similarities that other programs for protein structure comparison do not consistently point out and overall identified a larger number of structurally similar MFSs. MetalS² supports the comparison of MFSs harboring different metals and/or with different nuclearity and is available both as a stand-alone program and a Web tool (http://metalweb.cerm.unifi.it/tools/metals2/)

Yearly count of the number of articles that mention the BioJava project (“Biojava”), the Biojava website, or cite the BioJava publications (Pocock 2000 [1], Holland 2008 [2] and Prlić 2012 [3]).

Data collected in December 2018 from Google Scholar (https://scholar.google.com).</p

Multiple structure alignment of circularly permuted lectins generated and visualized with BioJava.

Implementations of CE-CP and CE-MC were used for the structural alignment, visualized using the Jmol based structure panel (left), the multiple alignment panel (top right), and a Forester based dendrogram of structural similarities (bottom right).</p

Mapping genetic variations to three- dimensional protein structures to enhance variant interpretation: a proposed framework

The translation of personal genomics to precision medicine depends on the accurate interpretation of the multitude of genetic variants observed for each individual. However, even when genetic variants are predicted to modify a protein, their functional implications may be unclear. Many diseases are caused by genetic variants affecting important protein features, such as enzyme active sites or interaction interfaces. The scientific community has catalogued millions of genetic variants in genomic databases and thousands of protein structures in the Protein Data Bank. Mapping mutations onto three-dimensional (3D) structures enables atomic-level analyses of protein positions that may be important for the stability or formation of interactions; these may explain the effect of mutations and in some cases even open a path for targeted drug development. To accelerate progress in the integration of these data types, we held a two-day Gene Variation to 3D (GVto3D) workshop to report on the latest advances and to discuss unmet needs. The overarching goal of the workshop was to address the question: what can be done together as a community to advance the integration of genetic variants and 3D protein structures that could not be done by a single investigator or laboratory? Here we describe the workshop outcomes, review the state of the field, and propose the development of a framework with which to promote progress in this arena. The framework will include a set of standard formats, common ontologies, a common application programming interface to enable interoperation of the resources, and a Tool Registry to make it easy to find and apply the tools to specific analysis problems. Interoperability will enable integration of diverse data sources and tools and collaborative development of variant effect prediction methods