CirPred

CirPred models circularly permuted (CP) and co-linear protein structures to support protein engineering by predicting permutant conformations and designing connection linkers.

Key Features:

• Circular permutation (CP) modeling: Predicts structures of proteins after native termini are connected and new termini are created at alternate sites.
• Co-linear protein structure modeling: Performs traditional co-linear structural modeling alongside CP modeling.
• Structure prediction of alternative conformations: Predicts permutant conformations that can be distinct from native forms, including conformations resulting from 3D domain swapping.
• Low sequence-identity permutant modeling: Maintains predictive capability for permutants exhibiting low sequence identity to their native counterparts.
• Linker design (subangstrom accuracy): Designs connection linkers between new termini with reported subangstrom accuracy.
• 3D domain swapping identification: Detects occurrences of three-dimensional domain swapping induced by circular permutation.

Scientific Applications:

• Protein engineering: Supports engineering of proteins by enabling exploration of alternative termini placements and linker choices.
• Design of novel functions and properties: Facilitates design efforts aimed at producing proteins with altered or novel activities through permutation and linker modification.
• Analysis of structural dynamics: Enables study of conformational changes and 3D domain swapping that affect protein structure and function.
• Experimental planning to reduce trial-and-error: Informs selection of permutation sites and linker designs to decrease experimental iteration in CP projects.

Methodology:

Performs circularly permuted and co-linear protein structure modeling, applies a linker-design algorithm with reported subangstrom accuracy, and identifies 3D domain swapping in permutants.