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The ITS2 Database

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FireProtASR: A Web Server for Fully Automated Ancestral Sequence Reconstruction.

Milos Musil¹, Rayyan Tariq Khan¹, Andy Beier¹

¹Loschmidt Laboratories, Masaryk University.

Briefings in Bioinformatics

|December 21, 2020

Summary

This study introduces FireProtASR, an automated tool for ancestral sequence reconstruction. It simplifies designing highly stable proteins for biotechnology and biomedical applications by requiring only a sequence query.

Keywords:

ancestral enzymes ancestral sequence reconstruction evolution phylogeny-based analysis protein stability

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Application of I TASSER, trRosetta, UCSF Chimera, HADDOCK server, and HEX loria for De Novo and In Silico Design of Proteins

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Published on: July 8, 2025

Area of Science:

Biochemistry
Computational Biology
Protein Engineering

Background:

Native proteins often lack stability for industrial applications due to their evolution under mild conditions.
Ancestral sequence reconstruction (ASR) is a method to infer evolutionary history and design more stable proteins.
Existing ASR tools require significant user expertise in data preparation.

Purpose of the Study:

To develop a fully automated workflow for ancestral sequence reconstruction.
To make ASR accessible to users with limited experience.
To facilitate the design of highly stable proteins for various applications.

Main Methods:

Developed FireProtASR, a computational workflow for automated ASR.
Integrated an interactive and user-friendly web interface.
The only input required is a protein sequence query.

Main Results:

FireProtASR successfully automates the process of obtaining ancestral sequences.
The tool enables users, even inexperienced ones, to perform ASR.
Provides a streamlined approach to designing stable proteins.

Conclusions:

FireProtASR overcomes previous obstacles in ASR accessibility.
The tool democratizes the design of engineered proteins with enhanced stability.
FireProtASR is freely available, promoting wider research and application.