Improving Pairwise Sequence Alignment between Distantly Related Proteins

Sequence alignment between remotely related proteins has been one of the more difficult problems in structural biology. Improvements have been achieved by incorporating information that enhances the diversity of the substitution matrices. NdPASA is a web-based server that optimizes sequence alignments between proteins sharing low percentages of sequence identity. The program integrates structure information of the template sequence into a global alignment algorithm by employing amino acids’ neighbor-dependent propensities for secondary structure as unique parameters for alignment. NdPASA optimizes alignment by evaluating the likelihood of a residue pair in the query sequence matching against a corresponding residue pair adopting a particular secondary structure in the template sequence. The server is designed to aid homologous protein structure modeling. It is most effective when the structure of the template sequence is known. NdPASA can be accessed online at http://www.fenglab.org/bioserver.html .