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ABSTRACT: Hidden Markov models were used to identify recurrent short 3D structural building blocks (SSBBs) describing protein backbones.
Polypeptide chains were broken down into successive short segments defined by their inter-alpha-carbon distances. Fitting
the model to a database of nonredundant proteins identified 12 distinct SSBBs and described the preferred pathways by which
SSBBs were assembled to form the 3D structure of the proteins. Protein backbones were labelled in terms of these SSBBs. The
observed SSBB preferences for fragments located between regular secondary structures suggested that they depended more on
the following regular structure than on the preceding one. Extraction of repeated series of SSBBs between regular secondary
structures showed some structural specificity within different connection types. These results confirm that SSBBs can be used
as building blocks for analyzing protein structures, and can yield new information on the structures of the coils flanking
secondary structures.
Theoretical Chemistry Accounts 01/1999; 101(1):33-40. · 2.16 Impact Factor
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ABSTRACT: Complete genomic sequences will become available in the future. New methods to deal with very large sequences (sizes beyond 100 kb) efficiently are required. One of the main aims of such work is to increase our understanding of genome organization and evolution. This requires studies of the locations of regions of similarity.
We present here a new tool, ASSIRC ('Accelerated Search for SImilarity Regions in Chromosomes'), for finding regions of similarity in genomic sequences. The method involves three steps: (i) identification of short exact chains of fixed size, called 'seeds', common to both sequences, using hashing functions; (ii) extension of these seeds into putative regions of similarity by a 'random walk' procedure; (iii) final selection of regions of similarity by assessing alignments of the putative sequences. We used simulations to estimate the proportion of regions of similarity not detected for particular region sizes, base identity proportions and seed sizes. This approach can be tailored to the user's specifications. We looked for regions of similarity between two yeast chromosomes (V and IX). The efficiency of the approach was compared to those of conventional programs BLAST and FASTA, by assessing CPU time required and the regions of similarity found for the same data set.
Source programs are freely available at the following address: ftp://ftp.biologie.ens. fr/pub/molbio/assirc.tar.gz
vincens@biologie.ens.fr, hazout@urbb.jussieu.fr
Bioinformatics 02/1998; 14(8):715-25. · 5.47 Impact Factor
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ABSTRACT: The GM immunoglobulin (Ig) allotype distributions of 49 native Amerindian populations from North to South America were analysed by a new technique called 'Mobile Sites Method' (MSM). This allows the global interpretation of genetic diversity in space by means of a distorted geographic map called a 'genetic similarity map'. This approach has been improved by superimposing in the distorted geographic map both the haplotype set (represented by hypothetical populations having a 100% frequency of the haplotype considered) and the 'geography-genetics discontinuities' (i.e. the zones between homogeneous population clusters). This bidimensional representation completes the interpretation of the genetic distances between populations in terms of local genetic diversity and possible migrations. Our results concerning the spatial distribution of the Amerindian populations show: (i) a great interdependence of the geographic locations and the GM haplotype distributions (the importance of the geographic factor was checked with the usual technique of 'random sampling' and the percentage of explained distance variability decreases from 78% with the observed data to a level less than 67% with the random data); (ii) a parallelism between genetics and linguistics groups as indicated by the population clusters in the similarity map, and (iii) a complex distorted map revealing the presence of multiple population migrations and admixtures in the course of time. A particular distortion of South America suggests possible migrations by sea along the western and eastern coasts of Central America, or multiple migration waves without population admixture across Central America.
Annals of Human Genetics 02/1997; 61(Pt 1):37-47. · 2.57 Impact Factor
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ABSTRACT: The representation and display of protein surfaces are useful in many areas of molecular modeling, and surface shape study is particularly important in the analysis of protein-ligand interactions. We introduce here the notion of the molecular surface convex hull, allowing the depth of any molecular surface point to be defined. A two-dimensional (2D) map, the iso-depth contour map, and a three-dimensional (3D) representation, the iso-depth lines, allow the topography of a molecular surface to be displayed in terms of knobs (high depth) and holes (low depth).
Journal of Molecular Graphics 10/1994; 12(3):162-8, 193.
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ABSTRACT: The differentiation of T Lymphocytes within the thymus is an important biological phenomenon during which these cell acquire their functions to further control the immune system. Numerous experiments under various conditions have been devised to understand the different mechanisms involved in this complex process. Nevertheless, interpretation of these experiments lead to still contradictory debatable hypotheses. Modelisation of this process through classical simulation methods cannot be envisaged because they are not adapted to modifications of the model structure, which is the point of interest. For these reasons, we proposed a new approach of automatic search for model. The program consists of four independent connected modules: The generator produces model, based on the rationale of formal grammars. Protocol and experimental data are stored in a set of experiments. The simulator using a protocol and a model provides simulated results. Finally, the supervisor by comparing simulated results and experimental data, adapts the model parameters to increase their fit and either chooses a new experiment to explore, or modifies the model structure. Change of the model structure is performed among still unexplored models according to their "promise" level, which is iteratively evaluated relatively to previously explored models through a proposed model distance. The generator is written in Prolog and the other modules in C++. The architecture of the program allows us to modify or complete a module without changing anything in the other modules. As a consequence, the proposed modeling approach conceived to study T lymphocyte differentiation within the thymus remains independent of this biological phenomenon and can be applied to other biological problems.
Acta Biotheoretica 10/1992; 40(2-3):205-20. · 1.47 Impact Factor
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Annals of the New York Academy of Sciences 02/1991; 628:420-32. · 3.15 Impact Factor
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