Sequence annotation of nuclear receptor ligand-binding domains by automated homology modeling

The quality of three-dimensional homology models derived from protein seque nces pro,ides an independent measure of the suitability of a protein sequen ce for a certain fold. We have used automated homology modeling and model a ssessment tools to identify putative nuclear hormone receptor ligand-bindin g domains in the genome of Caenorhabditis elegans. Our results indicate tha t the availability of multiple crystal structures is crucial to obtaining u seful models in this receptor family. The majority of annotated mammalian n uclear hormone receptors could be assigned to a ligand-binding domain fold by using the best model derived from any of four template structures, This strategy also assigned the ligand-binding domain fold to a number of C.eleg ans sequences without prior annotation. Interestingly, the retinoic acid re ceptor crystal structure contributed most to the number of sequences that c ould be assigned to a ligand-binding domain fold. Several causes for this c an be suggested, including the high quality of this protein structure in te rms of our assessment tools, similarity between the biological function or ligand of this receptor and the modeled genes and gene duplication in C.ele gans.