Clustering of proximal sequence space for the identification of protein families

Motivation: The study of sequence space, and the deciphering of the structure of protein families and subfamilies, has up to now been required for work in comparative genomics and for the prediction of protein function. With the emergence of structural proteomics projects, it is becoming increasingly important to be able to select protein targets for structural studies that will appropriately cover the space of protein sequences, functions and genomic distribution. These problems are the motivation for the development of methods for clustering protein sequences and building families of potentially orthologous sequences, such as those proposed here. Results: First we developed a clustering strategy (Ncut algorithm) capable of forming groups of related sequences by assessing their pairwise relationships. The results presented for the ras super-family of proteins are similar to those produced by other clustering methods, but without the need for clustering the full sequence space. The Ncut clusters are then used as the input to a process of reconstruction of groups with equilibrated genomic composition formed by closely-related sequences. The results of applying this technique to the data set used in the construction of the COG database are very similar to those derived by the human experts responsible for this database.