Project: Metal binding environments in macromolecular structures Abstract: Metal ions play vital roles in both the mechanism and architecture of biological macromolecules, including the catalysis of biochemical reactions, electron transport, binding of gases, and stabilization of nucleotides and other polyphosphate compounds. However, a recent survey of publicly available structures of metal-containing proteins and nucleic acids deposited in the PDB revealed an abundance of misidentified and/or sub-optimally modeled metal binding sites. This prompted the creation of a diagnostic tool for the models of metal binding microenvironments, the CheckMyMetal (CMM) web server (, which detects geometric and other irregularities in structures of metal binding sites and alerts researchers to potential errors in metal assignment. As the production version of CMM has gained widespread usage, the research community has identified several directions for future development of major interest:1) investigate and validate uncommon heavy metal binding sites in macromolecular structures; 2) establish a server to provide customized subsets of high-quality, validated metal binding sites; 3) develop tools to automatically detect likely metal binding sites in electron density, and identify and add the most probable metal ion during crystallographic model building and refinement; and 4) systematically catalog metal binding architectures and detect new metal binding motifs. The toolkit we propose to develop, using CMM as a basis, contains several modules that will work either independently or as integrated steps in the structure modeling, validation, interpretation and annotation pipeline. This proposal was designed not only for structural biologists to model and validate new structures during crystallographic model building and refinement, but also for a broader audience?biomedical researchers studying metal-containing proteins and nucleic acids.

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Project: Metal binding environments in macromolecular structures Project Narrative: Metal ions such as iron, magnesium and zinc are crucial to life?many proteins and DNA/RNA macromolecules require these elements for numerous essential chemical and biophysical processes. Properly identifying and modeling metal ions are macromolecular atomic structures is not trivial, yet the scientific tools that support reliable analysis of metal ion binding sites are few, limited, and immature. Based on an established server used to check the quality of metal ion binding environment in macromolecules, we propose to develop a toolkit that will benefit many areas of research on structures of metal-containing proteins and nucleic acids, including validation, modeling, classification, and motif detection.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Biodata Management and Analysis Study Section (BDMA)
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Smith, Ward
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University of Virginia
Schools of Medicine
United States
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Handing, Katarzyna B; Niedzialkowska, Ewa; Shabalin, Ivan G et al. (2018) Characterizing metal-binding sites in proteins with X-ray crystallography. Nat Protoc 13:1062-1090
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