Comparing protein structures: A Gaussian-based approach to the three-dimensional structural similarity of proteins

This study describes a new method for comparing three-dimensional protein structures based on an optimal alignment of their steric fields. The method is based upon the use of spherical Gaussian functions located on individual atoms. This representation generates a flexible description of the underlying fold geometry of proteins that can be adjusted by changing the ‘width’ of the Gaussians. Reducing the width sharpens the representation and leads to a more ‘atomlike’ description; increasing the width creates a fuzzier representation that preserves the general shape features of the chain fold but with a consequent loss in atomic resolution. The width used in this study is based upon the features of individual atoms and provides a representation that is quite robust with respect to the variety of geometric features typically encountered in the alignment process. In addition, a post-alignment analysis is performed that generates sequence alignments from the corresponding structure alignments. An example, based on five mammalian and fungal matrix metalloproteinase crystal structures (human fibroblast collagenase, neutrophil collagenase, stromelysin, astacin, and adamalysin), illustrates a number of features of the Gaussian-based approach. © 2001 by Elsevier Science Inc.