Improved genetic algorithm-based protein structure comparisons: pairwise and multiple superpositions.

Three major improvements to a previously described method for automatic protein structure comparison are described. First, a limit to translations for the rigid-body superposition is now assigned according to the dimensions of the structures being compared. Second, examination of the effect of the gap penalty on the derivation of a sequence alignment corresponding to a given structure superposition has led to a method to evaluate alternative structure-based sequence alignments. Third, the pairwise procedure has been generalized to multiple structure alignment. This implementation of rigid-body superposition can recognize well documented distant relationships which hitherto have required consideration of additional features and properties as well as those relationships between proteins of different sizes. A much larger common scaffold or framework between six globins can be extracted than that obtained using a standard algorithm for multiple structure superposition.