PROSCA: an online platform for humanized scaffold mining facilitating rational protein engineering.

Area of Science:

• Protein Engineering and Design
• Computational Biology
• Structural Bioinformatics

Background:

• Small, stable, and low-immunogenicity protein scaffolds are crucial for protein engineering.
• Existing computational tools lack the ability to mine these specific scaffolds from large protein structure databases.

Purpose of the Study:

• To develop a structure-based online platform, PROSCA, for discovering novel, privileged protein scaffolds from the human proteome.
• To provide a tool for identifying protein scaffolds with potential engineering value.

Main Methods:

• PROSCA accepts protein structure inputs for alignment against the human proteome (experimental or AlphaFold2 predicted structures).
• The platform identifies structurally similar humanized protein scaffolds.
• It provides associated data including families, sequences, structures, and tissue expression levels.

Main Results:

• PROSCA enables exploration of the human proteome to discover previously unrecognized protein scaffolds.
• The platform offers interactive visualization of protein structures and expression data.
• Users can download customized results for further analysis.

Conclusions:

• PROSCA facilitates the identification of valuable protein scaffolds for rational protein design.
• The platform supports advanced protein engineering and selection technologies.
• PROSCA is a freely available resource for the scientific community.