Structural bioinformatics

Current status
Structural bioinformatics is an important contributor to understanding the molecular basis of biology and medicine, since structure(s) define the function of each biological agent. The resolved biomacromolecular structures are stored in worldwide Protein Data Bank (wwPDB), whose European part PDB Europe (PDBe) is an ELIXIR core data resource. Biologically important data related to the structures are accumulated in PDBe-Knowledge Base (PDBe-KB).

Structural bioinformatics is traditionally strong in the Czech Republic due to historical links to the PDB database, top-class X-ray, NMR and Cryo-EM groups, and groups developing structural bioinformatics software tools and databases used worldwide. ELIXIR CZ initiated the formation of the ELIXIR 3D-Bioinfo community and is deeply involved in the activities of this community.

Key domains and services in ELIXIR CZ are:

  • The visualization of biomacromolecular structures, including their experimental data and annotations. In this field, we develop the LiteMol suite (and its follow-up Mol*) for the visualization of biomacromolecules and CoordinateServerDensityServer and PatternQuery for fast data delivery.
  • Analysis of biomacromolecular structures, e.g. the detection, characterization and storing of information about channels and pores in biomacromolecules (MOLECaverCaverDockChannelsDB), prediction of ligand binding sites from protein structure (PrankWeb) and the validation of biomacromolecular structures (ValTrendsDBValidatorDBMotiveValidator, and
  • Protein engineering tools, supporting the design of protein variants with improved functionalities. Specifically, we develop tools for the construction of smart libraries for the screening (HotSpot Wizard), improvement and evaluation of protein stability (FireProt), solubility (SoluProt), and their effect on function (PredictSNP), and newly also on personalized medicine in oncology (PredictSNP onco).
  • Nucleic acid structure research, e.g., the formulation of community-accepted benchmarks that integrate the different levels of nucleic acid structure descriptions and the development of tools for the modelling, refinement, validation, and annotation of nucleic acid structures. We provide tools at the website for the analysis of nucleic acid structures. Moreover, we focus on the examination of structure-function relationships in RNAs with special attention on sn- and ncRNAs and develop the tools rPredictor and cpPredictorrboAnalyzer for this field.

Some of the ELIXIR CZ services are used daily by the life science community, and they are a direct part of PDBe or are integrated into PDBe-KB or PDBsum (i.e., LiteMol suiteMol*ChannelsDBPrankWebValidatorDB). The remaining services deal with PDBe and PDBe-KB data. The providers of these services are integrated or collaborate with the 3D-Bioinfo community.

ELIXIR CZ will serve as a platform for the Czech structural bioinformatics community where the national groups can work together to strengthen international visibility, training and established collaborations with PDBe and other ELIXIR core resources.

Challenges and goals of ELIXIR CZ
Currently, the main challenges in structural bioinformatics are dealing with extra-large biomacromolecular structures (e.g., viruses, hybrid models, organelle models) including additional experimental data, the integration of huge sets of information about structure properties via structure annotation, and interconnection with other structural databases (ligands, nucleic acids, glycans, etc.).

ELIXIR CZ strategic goals in Structural Bioinformatics are as follows:

  1. Goal 1: Evolve and progress the key ELIXIR CZ domains and services by:
    • Raising the quality of existing tools and databases to enrich their robustness, stability, interoperability, FAIRification and effectivity
    • Extending ELIXIR CZ tools and databases to handle the above-mentioned challenges, i.e.:
      • Ability to process extra-large and hybrid structures
      • Ability to utilize annotations consolidating results from multiple methods via collaboration with ELIXIR core resources such as PDBe-KB
  2. Goal 2: Work on activities and the growth of the ELIXIR 3D-Bioinfo community in accord with the 3D-Bioinfo White paper and interact with its members via publications and joint grants
  3. Goal 3: Synergy identification and branding:
    • The identification of strong synergies between ELIXIR CZ structural bioinformatics research groups and their activities in the context of their national and international connections to research communities (e.g., Instruct-ERICiNEXT-DiscoveryEUOPENSCREEN and BioExcel) and ELIXIR platforms and communities
    • Branding of ELIXIR CZ structural bioinformatics services (e.g. their identification on the ELIXIR CZ website, at and on the webpages of the tools, joint scientific papers about workflows, inputs in social media)