SFESA

SFESA refines pairwise protein sequence alignments by integrating profile-based sequence scores and structure-derived residue-contact scores to improve alignment accuracy for homology modeling, particularly with distantly related templates.

Key Features:

• Local Shifts of Secondary Structures: Generates alignment variants by locally shifting secondary-structure elements defined in a template protein.
• Profile-based Sequence Score: Evaluates sequence similarity using profile information to account for conserved residues.
• Structure Score from Residue Contacts: Assesses structural compatibility using spatial residue-contact data derived from the template structure.
• Combined Scoring and Selection: Ranks candidate alignments by combining profile-based and structure scores and selects the highest-scoring variant as the refined alignment.

Scientific Applications:

• Homology Modeling: Improves target-to-template alignments to increase the accuracy of homology-derived protein structure models.
• Structure Prediction for Distant Homologs: Enhances alignment quality between distantly related sequences and templates to support more reliable structure prediction.
• Sequence-to-Structure Mapping for Functional Inference: Produces more accurate sequence-to-structure mappings that facilitate downstream functional interpretation of protein models.

Methodology:

SFESA generates multiple alignment variants by locally shifting secondary-structure elements in the template, computes a profile-based sequence score and a structure score from template residue contacts for each variant, and selects the variant with the highest combined score as the refined alignment.