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D Gautheret

Publications and source records attributed to D Gautheret.

25 records · Page 2Linked to original sources
PubMed1993

Reproducing the three-dimensional structure of a tRNA molecule from structural constraints.

The three-dimensional structure of yeast tRNA(Phe) was reproduced at atomic resolution with the automated RNA modeling program MC-SYM, which is based on a constraint-satisfaction algorithm. Structural constraints used in the modeling were derived from the secondary structure, four tertiary base pairs, and other information available prior to the determination of the x-ray crystal structure of the tRNA. The program generated 26 solutions (models), all of which had the familiar "L" form of tRNA and root-mean-square deviations from the crystal structure in the range of 3.1-3.8 A. The interaction between uridine-8 and adenosine-14 was crucial in the modeling procedure, since only this among the tertiary pairs is necessary and sufficient to reproduce the L form of tRNA. Other tertiary interactions were critical in reducing the number of solutions proposed by the program.

Base Sequence↗
PubMed1993

Modeling the three-dimensional structure of RNA using discrete nucleotide conformational sets.

The flexibility about seven torsion angles in nucleotides constitutes a severe obstacle to computer modeling of RNA. The computational feasibility of RNA conformational searches can be enhanced by assigning to each nucleotide a set of discrete conformations. In this work, four types of discrete conformational sets for the atomic representation of nucleotide structures were defined and evaluated. These sets, comprising between 10 and 30 conformations, were tested for their ability to reproduce known RNA structures and to generate structures responding to new specifications. Conformational searches were performed with the MC-SYM program, which allows for the generation of all structures satisfying a predetermined set of three-dimensional constraints in a given discrete space. Results with known hairpin loop structures show that root-mean-square deviations of about 1.5 A for backbone atoms and about 2.0 A for all atoms between the modeled and X-ray crystal structures can be expected. The conformational set that gives the most faithful representation of test structures is based on the classification of nucleotide conformations derived from a structural database. Representative conformations are selected from each class that adequately sample variations in backbone direction, sugar pucker and base orientation. With this conformational set, most of the important features of test hairpin structures are reproduced with fidelity, indicating that biologically useful models can be constructed from the combination of discrete nucleotide conformations and an algorithm that rapidly and systematically scans the pre-defined conformational space.

Anticodon↗
PubMed1993

Modeling the three-dimensional structure of RNA.

The limited number of RNA structures determined by X-ray crystallography and NMR spectroscopy compels the use of experimental and theoretical methods that are less precise to obtain information on RNA conformation. RNA flexibility, a consequence of rotational freedom about seven intra- and internucleotide bonds, is unfortunately of such magnitude that these alternate techniques fall short of providing sufficient information to build robust tertiary structures. Various RNA modeling methods, described herein, permit the organization of this structural data to the form of three-dimensional structures. Interactive computer graphics techniques, for example, have generated several useful models. Also, conventional computer algorithms involving the minimization of empirical energy functions, previously limited to small molecules, are giving way to methods able to handle much larger molecules. Modified distance geometry and molecular mechanics algorithms, using simplified "pseudoatom" representations, can generate structures consistent with input data. A constraint satisfaction algorithm combined with discrete representations of nucleotide conformations systematically explores poorly defined regions of a molecule yielding all-atom representations, but requires enough structural constraints to avoid a computational explosion.

Algorithms↗
PubMed1991

The combination of symbolic and numerical computation for three-dimensional modeling of RNA.

Three-dimensional (3-D) structural models of RNA are essential for understanding of the cellular roles played by RNA. Such models have been obtained by a technique based on a constraint satisfaction algorithm that allows for the facile incorporation of secondary and other structural information. The program generates 3-D structures of RNA with atomic-level resolution that can be refined by numerical techniques such as energy minimization. The precision of this technique was evaluated by comparing predicted transfer RNA loop and RNA pseudoknot structures with known or consensus structures. The root-mean-square deviation (2.0 to 3.0 angstroms before minimization) between predicted and control structures reveal this system to be an effective method in modeling RNA.

Algorithms↗
PubMed1990

Pattern searching/alignment with RNA primary and secondary structures: an effective descriptor for tRNA.

A convenient pattern-matching program using primary and higher-order structural features has been developed based on a 'backtracking' algorithm. A second implementation of the algorithm uses descriptors of structural features (including primary sequences) to align a list of homologous or highly similar sequences. An application of the pattern matcher to the search for tRNA and group I intron structural motifs in sequence data banks is presented. The design of a highly discriminate tRNA motif, common to all cellular tRNAs and not found in a control sequence bank, was accomplished using the pattern matcher in conjunction with the alignment program.

Algorithms↗
PubMed1988

A secondary and tertiary structure editor for nucleic acids.

A major difficulty in the evaluation of secondary and tertiary structures of nucleic acids is the lack of convenient methods for their construction and representation. As a first step in a study of the symbolic representation of biopolymers, we report the development of a structure editor written in Pascal, permitting model construction on the screen of a personal computer. The program calculates energies for helical regions, allows user-defined helices and displays the secondary structure of a nucleic acid based on a user-selected set of helices. Screen and printer outputs can be in the form of a backbone or the letters of the primary sequence. The molecule can then be displayed in a format which simulates its three-dimensional structure. Using appropriate glasses, the molecule can be viewed on the screen in three dimensions. Other options include the manipulation of helices and single-stranded regions which results in changes in the spatial relationship between different regions of the molecule. The editor requires an IBM or compatible PC, 640 kbyte memory and a medium or high resolution graphics card.

Algorithms↗