PC_ali

PC_ali performs hybrid multiple structure and sequence alignments based on the structure+sequence similarity score PC_sim.

Key Features:

• Multiple Sequence Alignment Construction: PC_ali constructs protein MSAs either de novo or by modifying an input MSA, using a similarity matrix based on PC_sim.
• Starting MSA Generation: The program constructs a starting MSA based on the maximal cliques of the graph of pairwise alignments.
• Progressive Alignment Refinement: PC_ali refines the starting MSA through progressive alignments along a tree reconstructed with PC_div.
• Pairwise Similarity and Divergence Scores: Besides the MSA, PC_ali outputs pairwise similarity scores and divergence scores based on PC_sim.
• Phylogenetic Tree Output: PC_ali outputs a neighbor-joining phylogenetic tree obtained with the hybrid evolutionary divergence measure based on PC_sim.
• Superimposed Structures: PC_ali outputs a PDB file with multiply superimposed structures.
• Molecular Clock Violations: Optionally, PC_ali computes violations of the molecular clock for each pair of proteins.

Scientific Applications:

• Evolutionary Inference: PC_ali enables improved evolutionary inference for distantly related proteins by combining sequence and structure information.
• Distant Homolog Alignment: PC_ali addresses the problem of low-quality MSAs for distantly related proteins by leveraging the greater conservation of protein structure compared to sequence.
• Benchmark Alignment Comparison: PC_ali produces MSAs with higher similarity to reference MSAs such as Balibase compared to other tools.

Methodology:

PC_ali uses the hybrid protein sequence and structure similarity score PC_sim, defined as the main principal component of four correlated protein similarity measures: fraction of aligned residues, sequence identity, fraction of superimposed residues, and contact overlap. The corresponding divergence measure PC_div is derived from PC_sim. The program constructs a starting MSA from maximal cliques of the pairwise alignment graph and refines it through progressive alignments along the tree reconstructed with PC_div.