Simultaneous Alignment and Folding of Protein Sequences

Accurate comparative analysis tools for low-homology proteins remains a difficult challenge in computational biology, especially sequence alignment and consensus folding problems. We present

partiFold-Align

, the first algorithm for simultaneous alignment and consensus folding of unaligned protein sequences; the algorithm’s complexity is polynomial in time and space. Algorithmically,

partiFold-Align

exploits sparsity in the set of super-secondary structure pairings and alignment candidates to achieve an effectively cubic running time for simultaneous pairwise alignment and folding. We demonstrate the efficacy of these techniques on transmembrane

β

-barrel proteins, an important yet difficult class of proteins with few known three-dimensional structures. Testing against structurally derived sequence alignments,

partiFold-Align

significantly outperforms state-of-the-art pairwise sequence alignment tools in the most difficult low sequence homology case and improves secondary structure prediction where current approaches fail. Importantly,

partiFold-Align

requires no prior training. These general techniques are widely applicable to many more protein families.

partiFold-Align

is available at

http://partiFold.csail.mit.edu

.