GenProBiS

GenProBiS maps sequence variants onto protein structures from the Protein Data Bank (PDB) to define and characterize binding sites (protein–protein, protein–nucleic acid, protein–compound including glycosylation and other post-translational modifications, and protein–metal ion) and to assess variant impacts on binding.

Key Features:

• Mapping Sequence Variants: Maps human somatic missense mutations related to cancer and non-synonymous single nucleotide polymorphisms from 21 species onto approximately 80,000 PDB protein structures.
• Binding Site Types: Covers protein–protein, protein–nucleic acid, protein–compound (including glycosylation and other post-translational modification sites), and protein–metal ion binding sites.
• ProBiS-Based Identification: Defines binding sites by local structural comparisons of entire protein structures using the Protein Binding Sites (ProBiS) algorithm.
• ProBiS-Ligands Transposition: Transposes ligands from similar binding sites in other proteins to the query protein using an enhanced ProBiS-ligands approach.
• Three-Dimensional Binding-Site Grids: Generates three-dimensional grids of binding site surfaces that encompass the space occupied by predicted ligands.
• Deleterious Variant Identification: Identifies potentially deleterious sequence variants with implications for human and veterinary medicine and drug discovery.

Scientific Applications:

• Cancer Mechanism Analysis: Elucidates structural effects of somatic missense mutations in cancer on protein binding sites.
• Drug Discovery and Target Assessment: Identifies and characterizes potential drug-binding sites and evaluates how variants alter ligand interactions.
• Functional Annotation of Variants: Assesses impacts of non-synonymous SNPs across multiple species on protein–ligand and protein–macromolecule interactions.
• Hypothesis Generation and Experimental Design: Supports generation of mechanistic hypotheses about variant effects on protein function to inform experimental studies.

Methodology:

Maps sequence variants onto PDB structures; performs local structural comparisons using the Protein Binding Sites (ProBiS) algorithm; transposes ligands from similar binding sites via an enhanced ProBiS-ligands approach; generates three-dimensional binding-site surface grids representing space occupied by predicted ligands.