Use INTERCAAT Online

INTERCAAT: Identifying Interface Residues and Atomic Interactions Between Macromolecules

INTERCAAT is a geometry-based method that identifies interface residues and atomic interactions between protein chains in a PDB structure. It was developed by Steven Grudman, J Eduardo Fajardo and Andras Fiser at the Department of Systems and Computational Biology, Albert Einstein College of Medicine, and published in Bioinformatics in 2022. The authors state the source code is freely available.

Defining what counts as a protein interface is subjective. Some methods use solvent accessibility changes while others use distance thresholds, and the authors cite a study finding only about 80% residue overlap between any two interface prediction methods. INTERCAAT provides a generic, geometry-based alternative that considers interaction compatibility and exposes adjustable parameters.

How INTERCAAT Defines Interface Residues

1. Parse: read the PDB file.

2. Tessellate: build a Voronoi tessellation with each atom as a seed.

3. Define contacts: two atoms interact if they share a bounded hyperplane and are closer than the sum of their van der Waals radii plus the diameter of a solvent molecule.

4. Classify atoms: by coordinates and atom type rather than residue, so the approach applies to proteins, DNA, RNA and other molecules.

5. Filter for compatibility: keep only interactions between compatible atom classes, based on hydrophobic and hydrophilic properties.

6. Apply a residue threshold: a query residue is interface only if it has enough interactions with the partner chain(s).

INTERCAAT Benchmark Results Against Interface Databases

With no gold standard available, the authors compared against three databases of protein-protein interfaces.

As the minimum interaction requirement increased, recall decreased and precision increased. A minimum of 4 interactions gave the best balance, with F1 scores of about 0.8 against the other databases.

What is Tamarind Bio?

Tamarind Bio is a no-code bioinformatics platform built to give life scientists and researchers access to powerful computational tools. Many cutting-edge machine learning models are hard to deploy and use. Tamarind provides an intuitive, web-based environment that removes the complexity of high-performance computing, software dependencies and command-line interfaces.

The platform is designed for biologists, chemists and other researchers who may not have a background in programming or cloud infrastructure but want to run models on their own data. Key features include:

• A user-friendly graphical interface for setting up and launching experiments

• A robust API for integration into existing research pipelines

• An automated system for managing and scaling computational resources

Tamarind treats information and data security as a top priority, as detailed in its Trust Center and Terms of Service.

Accelerating Discovery with INTERCAAT on Tamarind Bio

• Interface mapping: list which residues of one chain contact a partner chain.

• Atomic interaction lists: obtain every atomic interaction with distances and atom classes.

• Interaction matrices: view the number of atomic interactions per interface residue.

• Beyond proteins: the authors describe possible support for nucleic acids and lipids in supplementary material.

How to Use INTERCAAT on Tamarind Bio

1. Open the tool: log in to tamarind.bio and open INTERCAAT.

2. Upload a structure: provide a PDB file.

3. Specify chains: the query chain ID and interacting chain ID(s).

4. Set options: minimum number of interactions (default benchmarked at 4), class compatibility, solvent radius, if exposed.

5. Run: submit the job.

6. Download outputs: atomic interactions and an optional interaction matrix.

7. Interpret: raise the threshold for precision or lower it for recall.

Things to Keep in Mind

• No gold-standard interface definition exists, so validation is comparative.

• Benchmarks covered only protein-protein interactions.

• Only eight atom types are recognized; unknown atoms get a default radius and are treated as universally compatible.

• Atoms are points for tessellation but spheres for distance cutoffs, which the authors call a minor inconsistency.

Source: Grudman S, Fajardo JE, Fiser A. INTERCAAT: identifying interface residues between macromolecules. Bioinformatics, 2022;38(2):554-555. DOI: 10.1093/bioinformatics/btab596. Code: https://gitlab.com/fiserlab.org/intercaat.