45,366 research outputs found
DALI and the persistence of protein shape
DALI is a popular resource for comparing protein structures. The software is based on distance-matrix alignment. The associated web server provides tools to navigate, integrate and organize some data pushed out by genomics and structural genomics. The server has been running continuously for the past 25 years. Structural biologists routinely use DALI to compare a new structure against previously known protein structures. If significant similarities are discovered, it may indicate a distant homology, that is, that the structures are of shared origin. This may be significant in determining the molecular mechanisms, as these may remain very similar from a distant predecessor to the present day, for example, from the last common ancestor of humans and bacteria. Meta-analysis of independent reference-based evaluations of alignment accuracy and fold discrimination shows DALI at top rank in six out of 12 studies. The web server and standalone software are available from .Peer reviewe
FFAS03: a server for profile–profile sequence alignments
The FFAS03 server provides a web interface to the third generation of the profile–profile alignment and fold-recognition algorithm of fold and function assignment system (FFAS) [L. Rychlewski, L. Jaroszewski, W. Li and A. Godzik (2000), Protein Sci., 9, 232–241]. Profile–profile algorithms use information present in sequences of homologous proteins to amplify the patterns defining the family. As a result, they enable detection of remote homologies beyond the reach of other methods. FFAS, initially developed in 2000, is consistently one of the best ranked fold prediction methods in the CAFASP and LiveBench competitions. It is also used by several fold-recognition consensus methods and meta-servers. The FFAS03 server accepts a user supplied protein sequence and automatically generates a profile, which is then compared with several sets of sequence profiles of proteins from PDB, COG, PFAM and SCOP. The profile databases used by the server are automatically updated with the latest structural and sequence information. The server provides access to the alignment analysis, multiple alignment, and comparative modeling tools. Access to the server is open for both academic and commercial researchers. The FFAS03 server is available at
Resuscitation-promoting factors possess a lysozyme-like domain
The novel bacterial cytokine family – resuscitation-promoting factors (Rpfs) – share a conserved domain of uncharacterized function. Predicting the structure of this domain suggests that Rpfs possess a lysozyme-like domain. The model highlights the good conservation of residues involved in catalysis and substrate binding. A lysozyme-like function makes sense for this domain in the light of experimental characterization of the biological function of Rpfs
Composite structural motifs of binding sites for delineating biological functions of proteins
Most biological processes are described as a series of interactions between
proteins and other molecules, and interactions are in turn described in terms
of atomic structures. To annotate protein functions as sets of interaction
states at atomic resolution, and thereby to better understand the relation
between protein interactions and biological functions, we conducted exhaustive
all-against-all atomic structure comparisons of all known binding sites for
ligands including small molecules, proteins and nucleic acids, and identified
recurring elementary motifs. By integrating the elementary motifs associated
with each subunit, we defined composite motifs which represent
context-dependent combinations of elementary motifs. It is demonstrated that
function similarity can be better inferred from composite motif similarity
compared to the similarity of protein sequences or of individual binding sites.
By integrating the composite motifs associated with each protein function, we
define meta-composite motifs each of which is regarded as a time-independent
diagrammatic representation of a biological process. It is shown that
meta-composite motifs provide richer annotations of biological processes than
sequence clusters. The present results serve as a basis for bridging atomic
structures to higher-order biological phenomena by classification and
integration of binding site structures.Comment: 34 pages, 7 figure
FFAS server: novel features and applications.
The Fold and Function Assignment System (FFAS) server [Jaroszewski et al. (2005) FFAS03: a server for profile-profile sequence alignments. Nucleic Acids Research, 33, W284-W288] implements the algorithm for protein profile-profile alignment introduced originally in [Rychlewski et al. (2000) Comparison of sequence profiles. Strategies for structural predictions using sequence information. Protein Science: a Publication of the Protein Society, 9, 232-241]. Here, we present updates, changes and novel functionality added to the server since 2005 and discuss its new applications. The sequence database used to calculate sequence profiles was enriched by adding sets of publicly available metagenomic sequences. The profile of a user's protein can now be compared with ∼20 additional profile databases, including several complete proteomes, human proteins involved in genetic diseases and a database of microbial virulence factors. A newly developed interface uses a system of tabs, allowing the user to navigate multiple results pages, and also includes novel functionality, such as a dotplot graph viewer, modeling tools, an improved 3D alignment viewer and links to the database of structural similarities. The FFAS server was also optimized for speed: running times were reduced by an order of magnitude. The FFAS server, http://ffas.godziklab.org, has no log-in requirement, albeit there is an option to register and store results in individual, password-protected directories. Source code and Linux executables for the FFAS program are available for download from the FFAS server
Recommended from our members
Evolutionary and molecular foundations of multiple contemporary functions of the nitroreductase superfamily.
Insight regarding how diverse enzymatic functions and reactions have evolved from ancestral scaffolds is fundamental to understanding chemical and evolutionary biology, and for the exploitation of enzymes for biotechnology. We undertook an extensive computational analysis using a unique and comprehensive combination of tools that include large-scale phylogenetic reconstruction to determine the sequence, structural, and functional relationships of the functionally diverse flavin mononucleotide-dependent nitroreductase (NTR) superfamily (>24,000 sequences from all domains of life, 54 structures, and >10 enzymatic functions). Our results suggest an evolutionary model in which contemporary subgroups of the superfamily have diverged in a radial manner from a minimal flavin-binding scaffold. We identified the structural design principle for this divergence: Insertions at key positions in the minimal scaffold that, combined with the fixation of key residues, have led to functional specialization. These results will aid future efforts to delineate the emergence of functional diversity in enzyme superfamilies, provide clues for functional inference for superfamily members of unknown function, and facilitate rational redesign of the NTR scaffold
- …