The HHpred interactive server for protein homology detection and structure prediction

HHpred is a fast server for remote protein homology detection and structure prediction and is the first to implement pairwise comparison of profile hidden Markov models (HMMs). It allows to search a wide choice of databases, such as the PDB, SCOP, Pfam, SMART, COGs and CDD. It accepts a single query sequence or a multiple alignment as input. Within only a few minutes it returns the search results in a user-friendly format similar to that of PSI-BLAST. Search options include local or global alignment and scoring secondary structure similarity. HHpred can produce pairwise query-template alignments, multiple alignments of the query with a set of templates selected from the search results, as well as 3D structural models that are calculated by the MODELLER software from these alignments. A detailed help facility is available. As a demonstration, we analyze the sequence of SpoVT, a transcriptional regulator from Bacillus subtilis. HHpred can be accessed at .

[1]  Roland L. Dunbrack,et al.  CAFASP3: The third critical assessment of fully automated structure prediction methods , 2003, Proteins.

[2]  Ralf Zimmer,et al.  Profile-Profile Alignment: A Powerful Tool for Protein Structure Prediction , 2002, Pacific Symposium on Biocomputing.

[3]  W. Pearson.  Searching protein sequence libraries: comparison of the sensitivity and selectivity of the Smith-Waterman and FASTA algorithms. , 1991, Genomics.

[4]  A. Godzik,et al.  Sensitive sequence comparison as protein function predictor. , 1999, Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing.

[5]  Roland L. Dunbrack,et al.  CAFASP2: The second critical assessment of fully automated structure prediction methods , 2001, Proteins.

[6]  E. Myers,et al.  Basic local alignment search tool. , 1990, Journal of molecular biology.

[7]  Peer Bork,et al.  SMART: identification and annotation of domains from signalling and extracellular protein sequences , 1999, Nucleic Acids Res..

[8]  Thomas L. Madden,et al.  Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. , 1997, Nucleic acids research.

[9]  Daisuke Kihara,et al.  Microbial genomes have over 72% structure assignment by the threading algorithm PROSPECTOR_Q , 2004, Proteins.

[10]  Sean R. Eddy,et al.  Pfam: multiple sequence alignments and HMM-profiles of protein domains , 1998, Nucleic Acids Res..

[11]  Anna R Panchenko,et al.  Finding weak similarities between proteins by sequence profile comparison. , 2003, Nucleic acids research.

[12]  Nick V Grishin,et al.  Biochemical identification of Argonaute 2 as the sole protein required for RNA-induced silencing complex activity. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[13]  Benjamin A. Shoemaker,et al.  CDD: a database of conserved domain alignments with links to domain three-dimensional structure , 2002, Nucleic Acids Res..

[14]  Lvek,et al.  Evolution of protein structures and functions , 2022 .

[15]  S. Burley,et al.  Crystal structure of the MazE/MazF complex: molecular bases of antidote-toxin recognition. , 2003, Molecular cell.

[16]  Arne Elofsson,et al.  3D-Jury: A Simple Approach to Improve Protein Structure Predictions , 2003, Bioinform..

[17]  W. Kabsch,et al.  Dictionary of protein secondary structure: Pattern recognition of hydrogen‐bonded and geometrical features , 1983, Biopolymers.

[18]  Leszek Rychlewski,et al.  Protein domain of unknown function DUF1023 is an α/β hydrolase , 2005 .

[19]  Golan Yona,et al.  Within the twilight zone: a sensitive profile-profile comparison tool based on information theory. , 2002, Journal of molecular biology.

[20]  Leszek Rychlewski,et al.  Protein domain of unknown function DUF1023 is an alpha/beta hydrolase. , 2005, Proteins.

[21]  Tran Cat Dong,et al.  DNA-binding studies on the Bacillus subtilis transcriptional regulator and AbrB homologue, SpoVT. , 2004, FEMS microbiology letters.

[22]  S. Pietrokovski.  Searching databases of conserved sequence regions by aligning protein multiple-alignments. , 1996, Nucleic acids research.

[23]  N. Grishin,et al.  COMPASS: a tool for comparison of multiple protein alignments with assessment of statistical significance. , 2003, Journal of molecular biology.

[24]  Daniel Fischer,et al.  3D‐SHOTGUN: A novel, cooperative, fold‐recognition meta‐predictor , 2003, Proteins.

[25]  A G Murzin,et al.  SCOP: a structural classification of proteins database for the investigation of sequences and structures. , 1995, Journal of molecular biology.

[26]  Leszek Rychlewski,et al.  Protein structure prediction for the male-specific region of the human Y chromosome. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[27]  Johannes Söding,et al.  Protein homology detection by HMM?CHMM comparison , 2005, Bioinform..

[28]  Ceslovas Venclovas,et al.  Structure-based predictions of Rad1, Rad9, Hus1 and Rad17 participation in sliding clamp and clamp-loading complexes , 2000, Nucleic Acids Res..

[29]  Annabel E. Todd,et al.  Evolution of function in protein superfamilies, from a structural perspective. , 2001, Journal of molecular biology.

[30]  Sean R. Eddy,et al.  Profile hidden Markov models , 1998, Bioinform..

[31]  Philip E. Bourne,et al.  The distribution and query systems of the RCSB Protein Data Bank , 2004, Nucleic Acids Res..

[32]  D T Jones,et al.  Protein secondary structure prediction based on position-specific scoring matrices. , 1999, Journal of molecular biology.

[33]  Janusz M. Bujnicki,et al.  Inference of relationships in the ‘twilight zone’ of homology using a combination of bioinformatics and site-directed mutagenesis: a case study of restriction endonucleases Bsp6I and PvuII , 2005, Nucleic acids research.

[34]  A. Godzik,et al.  Fold and function predictions for Mycoplasma genitalium proteins. , 1998, Folding & design.

[35]  T. Blundell,et al.  Comparative protein modelling by satisfaction of spatial restraints. , 1993, Journal of molecular biology.

[36]  K. Devine,et al.  Expression of AbrB, a transition state regulator from Bacillus subtilis, is growth phase dependent in a manner resembling that of Fis, the nucleoid binding protein from Escherichia coli , 1997, Journal of bacteriology.

[37]  Darren A. Natale,et al.  The COG database: an updated version includes eukaryotes , 2003, BMC Bioinformatics.