There are 2220 multi-member families and 1582 orphans (single-member families) consisting of about 20,000 domains in the current version of PALI. Over 200,000 pair-wise and 2220 multiple structural alignments have been generated for all multimember families. Every family with at least three members is associated with two dendrograms, one based on the structural dissimilarity metric (SDM) defined for every pair-wise superposition and the other based on the identity of the topologically equivalent residues. For orphan families, the domain level sequences are provided. Alignments of protein domains of known 3-D structure from PALI integrated with homologous sequences from UniProt (Universal Protein Resource) database [4,5] are also available for every family in PALI. PSI-BLAST search using a query sequence can be performed against the structural members in PALI, the structural members integrated with the sequence homologues from UniProt database (PALI+). All the pair-wise structural superposition were generated using DALI [6,7] program. Structure alignment program MUSTANG  was used to superimpose multiple homologous protein domain structures. A graphical interface (Jmol applet) for every family in PALI to view the structure based multiple alignment and pair-wise structural alignments is also provided. Integration of the domain sequences with UniProt database is achieved in the following two steps: Structure based multiple sequence alignments for each family are queried against Uniref90 using PSI-BLAST for 20 iterations and the hits obtained are filtered subsequently based on 70% query coverage and E-value of 0.0001. HMM profiles for each family are generated based on structure based multiple sequence alignment using hmmbuild (HMMER 3.0) . These profiles are used to obtain integrated sequence-structure alignments at the family level using hmmalign (HMMER 3.0). For orphan PALI families subsequent to PSI-BLAST runs the sequences are aligned using MAFFT .
In the current version (v2.8c), we have added ~300 new multi-membered families and 148 new orphan families to the previous version. These correspond to ~2500 new domains added to the multiple and pairwise structural alignments. These additions are a result of the SCOP update of 1.75C.
RMB is supported by Council of Scientific and Industrial Research, New Delhi and SM is supported by Indian Institute of Science, Bangalore.
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