LPTD

LPTD determines protein topology from medium-resolution cryo-electron microscopy (cryo-EM) maps by matching sequence-derived secondary structure elements (α-helices and β-sheets) to density-derived SSEs to identify native topologies.

Key Features:

• Secondary structure element matching: Identifies and matches α-helices and β-sheets between protein sequence and cryo-EM density maps.
• Graph transformation: Formulates the SSE matching problem as a complete weighted bipartite graph matching problem in three-dimensional geometrical space.
• Distance-based scoring: Uses a distance-based scoring function to evaluate and score SSE correspondences.
• Sequence-derived features: Leverages features extracted from the protein sequence to inform matching.
• Linear programming algorithm: Applies a linear programming–based algorithm as a decision-making strategy to discern the native topology among candidate configurations.
• Scalability: Capable of handling large proteins with up to 65 SSEs.
• Performance: Recovers the native topology as the first-ranked solution in >77% of cases within <2 seconds.
• Validation datasets: Evaluated on experimental and simulated datasets comprising 12 α-β proteins and 15 simulated cases.

Scientific Applications:

• Protein topology determination: Determination of protein topology from medium-resolution cryo-EM maps.
• SSE assignment for model building: Assignment of α-helices and β-sheets between sequence and density to support construction of atomic-level structures.
• Large complex protein analysis: Analysis of large proteins containing many SSEs (up to 65 SSEs).
• Method benchmarking: Benchmarking and validation of topology prediction methods using experimental and simulated datasets (12 α-β proteins and 15 simulated cases).

Methodology:

Transforms SSE matching into a complete weighted bipartite graph matching problem in three-dimensional geometrical space, uses features extracted from the protein sequence and a distance-based scoring function to weight correspondences, and applies a linear programming–based algorithm to select the native topology among candidate configurations.