Welcome to HMMology3D – Your Gateway to Structural Homology

HMMology3D is a web application designed to identify and analyze homologous proteins using structure-based Hidden Markov Models (HMMs) generated from Foldseek-derived 3Di sequences. Users can provide a list of PDB Chain IDs or a tar file containing individual PDB files comprising single chains. By leveraging multiple queries within an HMM, this service enhances the chances of detecting homologs compared to single pairwise structure searches, much like sequence-based homology searches. The results returned (hits) are annotated with comprehensive information from Uniprot, SCOP, CATH, ECOD, Pfam, and NCBI Taxonomy, offering a rich contextual understanding of detected homologs. Results are presented in a user-friendly way. Interested in looking up homologs?

Figure: Protein structures provided as input are coverted to their respective 3Di sequences using Foldseek. An alignment is constructed using the 3Di substitution matrix. A profile HMM is generated which is then used to identify 3Di sequences representing structures in RCSB PDB. Hits generated are annotated and the results are returned to the user.