Effective inter-residue contact definitions for accurate protein fold recognition

Area of Science:

• Computational biology
• Structural bioinformatics
• Protein science

Background:

• Effective encoding of residue contact information is crucial for accurate protein structure prediction.
• Residue contacts capture long-range interactions, outperforming other scoring terms.
• Evaluating various contact definitions is essential for optimizing template-based protein structure prediction.

Purpose of the Study:

• To determine the most effective definition of residue contacts for template-based protein structure prediction.
• To assess the impact of different contact definitions and distance cutoffs on fold recognition accuracy.
• To investigate how alignment accuracy influences residue contact identification and fold recognition.

Main Methods:

• Evaluation of 45 different residue contact definitions.
• Systematic variation of contact bases and distance cutoffs.
• Assessment of fold recognition accuracy using identified residue contacts.

Main Results:

• Residue contact patterns best distinguish protein folds when Cβ-Cβ distances are ≤7.0 Å.
• Inaccurate threading alignments significantly reduce fold recognition accuracy by affecting common contact identification.
• Optimal contact definitions are fold-specific; larger cutoffs aid secondary structure spatial arrangement, while Cα-Cα is better for neighboring β strands.

Conclusions:

• The Cβ-Cβ distance of 7.0 Å provides the best overall performance for identifying proteins of the same fold.
• Tailoring residue contact definitions to specific protein folds can enhance threading performance.
• Fold-specific contact definitions are crucial for improving protein structure prediction accuracy.