EWCL Analytics

About EWCL

Entropy-Weighted Collapse Likelihood

A Next-Generation Framework for Protein Disorder & Collapse Analysis

EWCL (Entropy-Weighted Collapse Likelihood) is a biophysics-informed computational model for protein disorder, structural collapse risk, and entropy-aware pathogenicity analysis—engineered for speed, interpretability, and biological insight.

Scientific Foundation

EWCL quantifies, for every amino acid residue, the likelihood of entropic collapse using only static structure and sequence-derived data. No simulations, sequence alignments, or deep learning model training are required.

Core signals integrated:

  • Crystallographic B-factors: Experimental flexibility/instability
  • AlphaFold pLDDT: Structural confidence (benchmarking)
  • IUPred disorder: Intrinsic disorder propensity
  • Sequence features: Hydropathy, charge clusters, solvent exposure

Key advantage: Fully interpretable, computationally efficient, and grounded in entropy physics—not machine learning heuristics

Validation & Performance

EWCL undergoes extensive benchmarking across large, diverse protein datasets, capturing unique biophysical disorder and collapse signals—not simply mirroring existing predictors.

Current Validation Scale

>29,000 proteins validated

X-ray, AlphaFold, DisProt datasets

ClinVar pathogenic variants analysis

Monthly expansion of coverage

Final performance metrics and validation results published continuously with transparent methodology

Unique Advantages

No training data or sequence alignments required

Ultra-fast analysis (<2 seconds per 300 residues)

Residue-level interpretability with explicit entropy features

Unified analysis of disorder, flexibility, and mutation risk in one step

Physics-based output: captures ground-truth entropy, not proxy scores

Physics-based approach vs. machine learning heuristics or molecular simulations

How EWCL Works

1. Upload

PDB file, AlphaFold model, or sequence

2. Analyze

Automated per-residue entropy/collapse scoring

3. Visualize

3D structure, heatmaps, correlation plots

4. Compare

Benchmark against disorder/mutation databases

Typical runtime: <2 seconds per 300 residues

Platform Scope & Roadmap

Validated on:

>29,000 proteins, with ongoing monthly expansion

Current Features:

  • • Real-time structure scoring
  • • Interactive 3D visualization
  • • Hallucination detection
  • • JSON export (CSV in development)

In Progress:

  • • Expanded non-AlphaFold/X-ray support
  • • Updated ClinVar/DisProt ensemble metrics
  • • Refolding simulation pipeline
  • • API endpoints and Docker CLI

Philosophy & Acknowledgments

EWCL Philosophy:

A living scientific tool—continuously improved, transparently validated, and open about both its strengths and remaining challenges.

Special Recognition:

Professor Vladimir Uversky, whose foundational work on protein disorder and intrinsically disordered proteins directly inspired EWCL's development and validation roadmap.

Future Work & Integration

EWCL is actively expanding its capabilities to serve the scientific and clinical communities

Database Integration

DisProt Overlay:

Direct integration of DisProt disorder annotations, enabling real-time overlay and benchmarking of EWCL predictions against curated IDP datasets.

ClinVar Variant Mapping:

Automated mapping and visualization of ClinVar pathogenic variants on EWCL-predicted high-risk regions, supporting mutation risk interpretation and clinical variant screening.

Enhanced Analytics

Interactive Benchmark Panels:

Side-by-side comparison of EWCL results with B-factor, pLDDT, IUPred, and experimental annotations—facilitating in-depth structural and functional analysis.

User-Driven Validation:

Allowing users to upload custom protein sets and benchmark EWCL predictions against their own experimental or curated data.

Developer Resources

Publication-Ready Exports:

Support for downloadable, publication-quality figures (plots, heatmaps) and summary statistics in standard formats.

API & Programmatic Access:

RESTful endpoints and a Docker CLI for automated, large-scale EWCL analysis and integration into lab workflows.

Tutorials & Documentation:

Step-by-step guides, use-case examples, and full technical documentation for academic, research, and clinical users.

Coming Soon

Enhanced Integration

  • • DisProt and ClinVar overlays
  • • Enhanced visual analytics and interactive benchmarking
  • • Expanded validation across structural classes and clinical cohorts

Advanced Features

  • • Step-by-step tutorials & comprehensive documentation
  • • Use-case examples for academic & clinical applications
  • • Full technical API documentation and Docker deployment

Get Involved

EWCL is an open scientific initiative. We welcome collaborations, feedback, and contributions from the research community.