An Interface-Driven Design Strategy Yields a Novel, Corrugated Protein Architecture.

Area of Science:

• Protein engineering
• Computational biology
• Structural biology

Background:

• Designing proteins with novel folds is challenging due to unknown biophysical properties and lack of sequence profiles.
• Current computational protein design often focuses on recapitulating existing protein folds.

Purpose of the Study:

• To develop a new strategy for designing proteins with novel folds using intramolecular interfaces.
• To create a complex protein architecture with alternating handedness, departing from natural solenoid structures.

Main Methods:

• Interface-driven protein design strategy.
• Designing novel intramolecular interfaces to assemble protein fragments.
• Computational design and structural determination of novel proteins.

Main Results:

• Successfully designed three proteins with a novel, corrugated architecture featuring alternating handedness.
• Confirmed the computational design by solving the structures of two designed proteins.
• The interface-driven approach reduces computational sampling while maintaining topological control.

Conclusions:

• The developed interface-driven strategy is effective for designing proteins with novel folds and complex architectures.
• This method allows for the creation of non-natural protein structures, expanding the possibilities in protein engineering.
• The designed corrugated solenoid proteins demonstrate a new class of protein architecture achievable through computational design.