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Health-Universe/rascore-deploy
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A tool for analyzing RAS protein structures.

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Rascore is a tool for analyzing structures of the RAS protein family (KRAS, NRAS, and HRAS). The Rascore database presents a continually updated analysis of all available RAS structures in the Protein Data Bank (PDB) with their catalytic switch 1 (SW1) and switch 2 (SW2) loops conformationally classified and their molecular contents annotated (e.g., mutation status, nucleotide state, bound protein, inhibitor site).

Pages in the Rascore database include:

  • Home Page: Self explanatory.
  • Database Overview: Overview of the Rascore database, molecular annotations, and RAS conformational classification.
  • Search PDB: Search for individual PDB entries containing RAS structures.
  • Explore Conformations: Explore RAS SW1 and SW2 conformations found in the PDB by nucleotide state.
  • Analyze Mutations: Analyze the structural impact of RAS mutations by comparing WT and mutated structures.
  • Compare Inhibitors: Compare inhibitor-bound RAS structures by compound binding site and chemical substructure.
  • Query Database: Query the Rascore database by conformations and molecular annotations.
  • Classify Structures: Conformationally classify and annotate the molecular contents of uploaded RAS structures.

The Rascore database cannot be used to conformationally classify molecular dynamic simulations.

Details of our work are provided in the Cancer Research paper, Delineating The RAS Conformational Landscape. We hope that researchers will use Rascore to gain novel insights into RAS biology and drug discovery.

  • For many human cancers and tumor-associated diseases, mutations in the RAS isoforms (KRAS, NRAS, and HRAS) are the most common oncogenic alterations, making these proteins high-priority therapeutic targets.
  • Effectively targeting the RAS isoforms requires an exact understanding of their active, inactive, and druggable conformations.
  • In consequence, we analyzed over 700 available human KRAS, NRAS, and HRAS structures in the Protein Data Bank (PDB) to create a comprehensive map of the RAS conformational landscape.
  • First, we annotated the molecular contents of each RAS structure, including their mutation status, nucleotide state, and bound protein or inhibitor site (see right for key terms).
  • Second, we conformationally classified all available RAS structures based on the configurations of their catalytic switch 1 (SW1) and switch 2 (SW2) loops, identifying three SW1 and nine SW2 conformations.
  • The Rascore database presents a continually updated dataset of RAS structures in the PDB that are conformationally classified and annotated for their molecular contents (now 767 structures).
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Warning: App may appear to work well but has not been peer reviewed. Not intended for clinical use. Use with caution.


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Owner

Mitchell Parker

Member since