A2CA: Amino Acid Cluster Analysis

Open Beta – web version 2.0.42

Protein function emerges from a highly coupled three-dimensional scaffold in which substitutions can influence interactions far beyond an active or binding site. This complexity makes it difficult to distinguish residues that merely vary from positions constrained by structure, chemistry, or compensatory evolution, complicating both mechanistic interpretation and rational protein engineering. A2CA integrates multiple sequence alignments, phylogenetic trees, amino-acid physicochemical properties, optional protein structures, and pairwise coevolution analyses to place residue-level variation into an evolutionary context and help prioritize positions for experimental investigation.

Contact: Dr. Daniel Eggerichs

Interactions in a protein

How would you like to start?

Choose the entry point that matches your available data. A2CA can retrieve homologous proteins from a single sequence or protein structure with NCBI BLAST, generate an alignment and phylogeny from unaligned FASTA sequences, or start directly from a prepared alignment and tree.

Single sequence

Find homologs from a protein sequence or structure using NCBI BLAST.

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FASTA sequences

Align sequences and build a phylogenetic tree.

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Alignment & Tree

Upload a prepared alignment and phylogenetic tree.

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Continue a previous session:
Resources

The original R/Shiny implementation of A2CA is archived as: D. Eggerichs, D. Tischler; Science Data Bank (2023), DOI: www.doi.org/10.57760/sciencedb.09549.

Source code, version history, and future releases are maintained in the A2CA GitHub repository.

Software and services

  • MAFFT, executed on the A2CA server using the automatic strategy, for multiple-sequence alignment.
  • FastTree 2.1.11, loaded through BioWasm/Aioli, for browser-side phylogenetic tree inference.
  • 3Dmol.js 2.5.5 for interactive WebGL protein-structure visualization.
  • RCSB Protein Data Bank for retrieval of structures by PDB identifier.
  • NCBI BLAST Common URL API and NCBI Protein EFetch for homolog discovery and retrieval of cluster-representative protein sequences from a single query.
  • The A2CA interface and analyses use browser-native HTML, CSS, JavaScript, SVG, the File API, and WebGL. A small hosted Python backend provides same-origin access to NCBI and RCSB services and executes MAFFT.