A fragment-based protein interface design algorithm for symmetric assemblies.

Area of Science:

• Biochemistry and structural biology
• Computational biology and bioinformatics
• Materials science and engineering

Background:

• Protein engineering advances enable creating complex, novel protein assemblies for diverse applications.
• Designing interfaces for symmetric oligomeric protein components is challenging and not yet routine.
• Existing methods for protein docking differ from those required for symmetric assembly design.

Purpose of the Study:

• To develop a computational tool, nanohedra, to advance protein material engineering.
• To encode construction rules for symmetric material constructions within the software.
• To create algorithms for rapidly identifying favorable protein-protein interfaces.

Main Methods:

• Developed the nanohedra computer program incorporating construction rules for symmetric assemblies.
• Implemented algorithms for identifying favorable docking/interface arrangements using empirical protein fragment-pair associations.
• Generated candidate poses for amino acid interface design.

Main Results:

• Nanohedra generates highly native-like protein backbone poses.
• Generated poses meet the stringent requirements for symmetry-based assembly.
• Retrospective analysis suggests improved success rates for experimental studies.

Conclusions:

• Nanohedra facilitates the design of novel, symmetric protein assemblies.
• The program's approach enhances the likelihood of successful experimental outcomes.
• This work supports the emerging field of protein material engineering.