FrustratometeR

FrustratometeR computes local energetic frustration within protein structures to identify energetically frustrated regions relevant to protein function.

Key Features:

• Local Energetic Frustration Calculation: Quantifies local energetic frustration within protein structures, identifying regions that remain energetically frustrated after folding.
• Functional Annotation of Frustrated Sites: Maps frustrated regions to functional elements such as protein–protein interaction interfaces, small ligand recognition sites, catalytic residues, and allosteric regions.
• Molecular Dynamics Integration: Computes frustration metrics across molecular dynamics (MD) simulations and trajectories to assess temporal changes in energetic frustration.
• Point Mutant Analysis: Evaluates the effect of amino acid substitutions on local energetic frustration to assess mutation impacts.
• Scalability and Pipeline Integration: Supports large-scale analyses and integration into structural analysis pipelines for high-throughput studies.
• Implementation (R package): Implemented as an R package for local execution and integration into computational workflows.

Scientific Applications:

• Structural Biology: Identify and characterize frustrated regions associated with functional sites and conformational dynamics.
• Bioinformatics: Integrate frustration metrics into computational analyses and annotation pipelines for protein datasets.
• Computational Chemistry: Analyze energetic landscapes, ligand interactions, and the energetic basis of binding sites.
• Protein Dynamics and Function: Investigate relationships between local frustration and allostery, catalysis, and protein–protein interactions.
• Disease and Mutation Studies: Assess how amino acid variants alter local energetic frustration to explore molecular mechanisms of disease-related mutations.

Methodology:

Implemented as an R package, FrustratometeR computes local energetic frustration within protein structures, analyzes frustration across molecular dynamics simulations, and evaluates point mutant effects.