Biomedical subjects

A A Adzhubei

Publications and source records attributed to A A Adzhubei.

10 recordsLinked to original sources

PubMed2001

MDB: a database system utilizing automatic construction of modules and STAR-derived universal language.

MOTIVATION: The value of information greatly increases if stored in databases. The objective was to construct a multi-purpose database system primarily designed to store and provide access to three-dimensional structures of biological molecules including theoretical models. RESULTS: A dictionary defining data format and structure for three-dimensional models of biological molecules (MDB dictionary) was developed. The dictionary was written using universal, standardized data description language. This language can be applied to describe data with no restrictions on their origin or type, including metadata. Thus both the data definitions (format) and database descriptions are created using the uniform language and processed with universal software. A database and data design technique that allowed use of dictionaries to automatically construct relational databases was developed. This technique was employed to construct the MDB database system. Data design developed and applied in the MDB project makes it possible to carry out data curation utilizing the database engine to identify errors. It also allows storage and query of data at different levels of consistency with the standard format specifications, i.e. both the correctly formatted data, and data that requires further curation. AVAILABILITY: The MDB dictionary is available at http://www.gwer.ch/proteinstructure/mdb and as part of the PDB resources at http://pdb.rutgers.edu/mmcif/.

Computational Biology↗

PubMed1999

ISSD Version 2.0: taxonomic range extended.

Two more organisms from different taxonomic groups were added to a new version of the Integrated Sequence-Structure Database (ISSD). ISSD serves as an integrated source of sequence and structure information for the analysis of correlations between mRNA synonymous codon usage and three-dimensional structure of the encoded proteins. ISSD now holds 88 non-homologous Escherichia coli proteins and 25 yeast Saccharomyces cerevisiae proteins in addition to the expanded set of mammalian proteins, which includes 166 proteins (107 in ISSD Version 1.0). Comparison of ISSD sequences with organism-specific codon usage data derived from CUTG database shows that it is a representative subset of the GenBank coding sequences data. Preliminary results of the statistical analysis confirm that sequence-structure correlations observed by us earlier are also present in the upgraded ISSD (Version 2.0), including bacterial and yeast proteins. The ISSD Version 2.0 release includes an improved Web-based data search and retrieval system and is accessible via URL http://www.protein.bio.msu.su/issd/. ISSD can be also accessed at ExPASy, URL http://www.expasy.ch/swissmod/swiss-model.htm l

Animals↗

PubMed1998

An Integrated Sequence-Structure Database incorporating matching mRNA sequence, amino acid sequence and protein three-dimensional structure data.

We have constructed a non-homologous database, termed the Integrated Sequence-Structure Database (ISSD) which comprises the coding sequences of genes, amino acid sequences of the corresponding proteins, their secondary structure and straight phi,psi angles assignments, and polypeptide backbone coordinates. Each protein entry in the database holds the alignment of nucleotide sequence, amino acid sequence and the PDB three-dimensional structure data. The nucleotide and amino acid sequences for each entry are selected on the basis of exact matches of the source organism and cell environment. The current version 1.0 of ISSD is available on the WWW at http://www.protein.bio.msu.su/issd/ and includes 107 non-homologous mammalian proteins, of which 80 are human proteins. The database has been used by us for the analysis of synonymous codon usage patterns in mRNA sequences showing their correlation with the three-dimensional structure features in the encoded proteins. Possible ISSD applications include optimisation of protein expression, improvement of the protein structure prediction accuracy, and analysis of evolutionary aspects of the nucleotide sequence-protein structure relationship.

Algorithms↗

PubMed1996

Non-random usage of 'degenerate' codons is related to protein three-dimensional structure.

We report an analysis of a novel sequence-structure database of mammalian proteins incorporating nucleotide sequences of the exon regions of their genes together with protein sequence and structural information. We find that synonymous codon families (i.e. coding the same residue) have non-random codon distribution frequencies between protein secondary structure types. Their structural preferences are related to the third, 'silent' nucleotide position in a codon. We also find that some synonymous codons show very different or even opposite structural preferences at the N- or C-termini of structure fragments, relative to those observed for their amino acid residues.

Animals↗

PubMed1995

An approach to protein homology modelling based on an ensemble of NMR structures: application to the Sox-5 HMG-box protein.

A new approach has been developed to reduce multiple protein structures obtained from NMR structure analysis to a smaller number of representative structures which still reflect the structural diversity of the data sets. The method, based on the clustering of similar structures, has been tested in the homology model building of the structure of Sox-5, a sequence-specific DNA-binding protein belonging to the high mobility group (HMG) nuclear proteins family. Sox (SRY box) genes are the autosomal genes related to the sex-determining SRY, Y chromosomal gene. The Sox-5 protein, encoded by one of the SRY-related genes, displays a 29% sequence identity with the HMG1 B-box domain whose structure, determined previously by NMR, has been used in our study to predict the structure of Sox-5. Two independent ensembles of HMG1 structures, each represented by closely related coordinate sets, were used. Nine representative structures for HMG1 were subsequently selected as starting points for the modelling of Sox-5. The model of the protein shows close similarity to the HMG1 fold, with differences at the secondary structure level located mainly in alpha-helices 1 and 3. A left-handed, three residue per turn polyproline II helix, forming a conserved polyproline II/alpha-helix supersecondary motif, was identified in the N-terminal region of Sox-5 and other HMG boxes.

Algorithms↗

PubMed1994

Conservation of polyproline II helices in homologous proteins: implications for structure prediction by model building.

Left-handed polyproline II (PPII) helices commonly occur in globular proteins in segments of 4-8 residues. This paper analyzes the structural conservation of PPII-helices in 3 protein families: serine proteinases, aspartic proteinases, and immunoglobulin constant domains. Calculations of the number of conserved segments based on structural alignment of homologous molecules yielded similar results for the PPII-helices, the alpha-helices, and the beta-strands. The PPII-helices are consistently conserved at the level of 100-80% in the proteins with sequence identity above 20% and RMS deviation of structure alignments below 3.0 A. The most structurally important PPII segments are conserved below this level of sequence identity. These results suggest that the PPII-helices, in addition to the other 2 secondary structure classes, should be identified as part of structurally conserved regions in proteins. This is supported by similar values for the local RMS deviations of the aligned segments for the structural classes of PPII-helices, alpha-helices, and beta-strands. The PPII-helices are shown to participate in supersecondary elements such as PPII-helix/alpha-helix. The conservation of PPII-helices depends on the conservation of a supersecondary element as a whole. PPII-helices also form links, possibly flexible, in the interdomain regions. The role of the PPII-helices in model building by homology is 2-fold; they serve as additional conserved elements in the structure allowing improvement of the accuracy of a model and provide correct chain geometry for modeling of the segments equivalenced to them in a target sequence. The improvement in model building is demonstrated in 2 test studies.

Amino Acid Sequence↗

PubMed1993

Left-handed polyproline II helices commonly occur in globular proteins.

The main-chain conformations of 80 proteins were analysed to identify helical structures that commonly occur but do not fall into the known classes of alpha-helix, 3(10)-helix and beta-sheet. The analysis yielded 96 occurrences of four or more sequential residues forming the threefold left-handed poly-L-proline II (PPII) helix. This contradicts the previously held opinion that left-handed helices are rare in globular proteins. The main-chain dihedral angles of these helices form a cluster in phi,psi space that has a maximum at -75 degrees, 145 degrees, corresponding to conformations with the number of residues per turn (n) = -3.0. We show that 51% of PPII-helices lie within the range of n = -3.0(+/- 0.2). It is shown that the PPII segments are distinct from the conformation typical of beta-pleated sheets. Although proline residues commonly occurred in PPII-helices, this side-chain is not obligatory, as 28 of these helices did not contain proline. In addition, we found 120 segments with three C alpha atoms forming a PPII-helix. PPII-helices tend to occur on the surface of the protein and, having few main-chain hydrogen bonds with the rest of the protein, tend to be the more mobile segments of the molecule. The geometry of PPII helix allows the polypeptide chain to progress immediately from this conformation to right-handed alpha-helix and 3(10) helix, as well as to beta-sheet or reverse turn. We conclude that PPII-helices should be considered as a regular conformation and should be added to beta-sheets, alpha-helices and 3(10)-helices in databases of protein structures, in secondary structure prediction and in tertiary model-building.

Algorithms↗

PubMed1992

Tek FRODO: a new version of FRODO for Tektronix graphics stations.

A new version of the molecular graphics program FRODO was developed to allow the range of Tektronix graphics stations to be used for molecular modeling and crystallographic applications. The work was divided into two parts: first, the universal molecular modeling graphic package (Tek_MMGP) was written to enable basic modeling operations for Tektronix stations. Second, all routines of FRODO involving computer graphics were modified to fit the new hardware environment, and linked with Tek_MMGP. The resulting package, Tek_FRODO, has been used successfully for crystallographic refinement in several projects. The program, written in FORTRAN, is ready to be ported to any of Tektronix 3D graphics stations; it is available from the authors on request.

Computer Graphics↗

PubMed1987

Third type of secondary structure: noncooperative mobile conformation. Protein Data Bank analysis.

Analysis of 68 proteins from Protein Data Bank disclosed a new widely spread type of the secondary structure that is designated as mobile (M-) conformation. Helical parameters of M-conformation are close to the poly-L-proline II type helix. Its occurrence in globular proteins approximates that of the beta-sheet. The angles corresponding to the position of the M-conformation maximum in distribution of amino acid residues on a conformational map are phi: -65 degrees, psi: 140 degrees. Unique features and high occurrence in proteins make it possible to distinguish the M-conformation as an independent third type of the secondary structure in globular proteins, that should be included in the present classification.

Amino Acids↗

PubMed1987

Approaching a complete classification of protein secondary structure.

A complete classification of types of the protein secondary structure is developed on the basis of computer analysis of the crystallographic structural data deposited in the protein Data Bank. The majority of amino acid residues fall into five conformation types. A conclusion is drawn that the number of sequence variants of torsion angles phi, psi in globular proteins is limited and is essentially less than the number of possible amino acid sequences for this chain length. Along with alpha-helix and beta-structure, the distribution analysis assigning every maximum of distribution of amino acid conformations on Ramachandran map to a certain type of the secondary structure exposed a third type of the secondary structure that was previously neglected. This type of the structure is extended left-handed helical conformation, designated as mobile (M-) conformation. A full set of M-conformation fragments that seems to play a major role in protein globule dynamics has been obtained, a small radius of correlation for the polypeptide chain in M-conformation is demonstrated. It explains a prevalence of short segments of mobile conformation revealed in globular proteins. For secondary structure types, the frequency of occurrence of amino acid residues has been computed.

Amino Acids↗