Related Experiment Video
Updated: Sep 10, 2025

An Integrated Approach for Microprotein Identification and Sequence Analysis
Published on: July 12, 2022
An interpretable alphabet for local protein structure search based on amino acid neighborhoods
Saba Zerefa1, Jesse Cool2, Pramesh Singh3
1School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, United States.
Motivation:
Recent advancements in protein structure prediction methods have vastly increased the size of databases of protein structures, necessitating fast methods for protein structure comparison. Search methods that find structurally similar proteins can be applied to find remote homologs, study the functional relationships among proteins, and aid in protein engineering tasks.
Results:
We design a "3Dn" structural alphabet that encodes the local neighborhoods around each amino acid in an interpretable way. In a search benchmark task, a combination of our alphabet and Foldseek's 3Di alphabet, outperforms each alphabet individually and ranks best among local search methods that do not require amino acid identity information. We provide software tools that enable the exploration of novel alphabets and combinations of alphabets for protein structure search.
Availability And Implementation:
The code is freely available at https://github.com/spetti/structure_comparison and at Zenodo https://doi.org/10.5281/zenodo.15734371.
More Related Videos
Related Concept Videos
Protein Organization
The primary structure of a protein is its amino acid sequence....
Amino acids
Protein and Protein Structure
A protein's shape is critical to its function. For example, an enzyme...
Conservation of Protein Domains Over Different Proteins
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
Protein Folding
Conserved Binding Sites
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...

