ASSIGNING AMINO-ACID-SEQUENCES TO 3-DIMENSIONAL PROTEIN FOLDS

With the advent of genome sequencing projects, the amino acid sequence s of thousands of proteins are determined every year, Each of these pr otein sequences must be identified with its function and its 3-dimensi onal structure for us to gain a full understanding of the molecular bi ology of organisms, To meet this challenge, new methods are being deve loped for fold recognition, the computational assignment of newly dete rmined amino acid sequences to 3-dimensional protein structures, These methods start with a library of known 3-dimensional target protein st ructures, The new probe sequence is then aligned to each target protei n structure in the library and the compatibility of the sequence for t hat structure is scored, If a target structure is found to have a sign ificantly high compatibility score, it is assumed that the probe seque nce folds in much the same way as the target structure, The fundamenta l assumptions of this approach are that many different sequences fold in similar ways and there is a relatively high probability that a new sequence possesses a previously observed fold. We review various appro aches to fold recognition and break down the process into its main ste ps: creation of a library of target folds; representation of the folds ; alignment of the probe sequence to a target fold using a sequence-to -structure compatibility scoring function; and assessment of significa nce of compatibility. We emphasize that even though this new field of fold recognition has made rapid progress, technical problems remain to be solved in most of the steps. Standard benchmarks may help identify the problem steps and find solutions to the problems.