Protein structure alignment using a genetic algorithm

We have developed a novel, fully automatic method for aligning the three-di mensional structures of two proteins. The basic approach is to first align the proteins' secondary structure elements and then extend the alignment to include any equivalent residues found in loops or turns, The initial secon dary structure element alignment is determined by a genetic algorithm, Afte r refinement of the secondary structure element alignment, the protein back bones are superposed and a search is performed to identify any additional e quivalent residues in a convergent process. Alignments are evaluated using intramolecular distance matrices, Alignments can be performed with or witho ut sequential connectivity constraints. We have applied the method to prote ins from several cell-studied families: globins, immunoglobulins, serine pr oteases, dihydrofolate reductases, and DNA methyltransferases. Agreement wi th manually curated alignments is excellent. A web-based server and additio nal supporting information are available at http://engpub1.bu.edu/similar t o josephs. Proteins 2000;38:428-440. (C) 2000 Wiley-Liss, Inc.