Protein Sequence Alignment Analysis by Local Covariation: Coevolution Statistics Detect Benchmark Alignment Errors

Protein Sequence Alignment Analysis by Local Covariation: Coevolution Statistics Detect Benchmark Alignment Errors

The use of sequence alignments to understand protein families is ubiquitous in molecular biology. High quality alignments are difficult to build and protein alignment remains one of the largest open problems in computational biology. Misalignments can lead to inferential errors about protein structure, folding, function, phylogeny, and residue importance. Identifying alignment errors is difficu...

Identifying and Seeing beyond Multiple Sequence Alignment Errors Using Intra-Molecular Protein Covariation

BACKGROUND There is currently no way to verify the quality of a multiple sequence alignment that is independent of the assumptions used to build it. Sequence alignments are typically evaluated by a number of established criteria: sequence conservation, the number of aligned residues, the frequency of gaps, and the probable correct gap placement. Covariation analysis is used to find putatively i...

Local alignment statistics.

6.8 Local Sequence Alignment

log g i,j f(j) . For large n, the resulting PAM matrices often allow one to find related proteins even when there are practically no matches in the alignment. In this case, the underlying nucleotide sequences are so diverged that their comparison usually fails to find any statistically significant similarities. For example, the similarity between the cancer-causing ν-sis oncogene and the growth...

Flexible structural protein alignment by a sequence of local transformations

MOTIVATION Throughout evolution, homologous proteins have common regions that stay semi-rigid relative to each other and other parts that vary in a more noticeable way. In order to compare the increasing number of structures in the PDB, flexible geometrical alignments are needed, that are reliable and easy to use. RESULTS We present a protein structure alignment method whose main feature is t...