Walter B. Goad

Pattern recognition in nucleic acid sequences. I. A general method for finding local homologies and symmetries.

We present an algorithm--a generalization of the Needleman-Wunsch-Sellers algorithm--which finds within longer sequences all subsequences that resemble one another locally. The probability that so close a resemblance would occur by chance alone is calculated and used to classify these local homologies according to statistical significance. Repeats and inverted repeats may also be found. Results for both random and biological nucleic acid sequences are presented. Fourteen complete genomes are analyzed for dyad symmetries.

The GenBank genetic sequence databank

The GenBank Genetic Sequence Data Bank contains over 5700 entries for DNA and RNA sequences that have been reported since 1967. This paper briefly describes the contents of the database, the forms in which the database is distributed, and the services we offer to scientists who use the GenBank database.

CABIOS REVIEW The GenBank nucleic acid sequence database

The GenBank nucleic acid sequence database is a computer-based collection of all published DNA and RNA sequences; it contains over five million bases in close to six thousand sequence entries drawn from four thousand five hundred published articles. Each sequence is accompanied by relevant biological annotation. The database is available either on magnetic tape, on floppy diskettes, on-line or in hardcopy form. We discuss the structure of the database, the extent of the data and the implications of the database for research on nucleic acids.

Pattern recognition in nucleic acid sequences. II. An efficient method for finding locally stable secondary structures.

We present a method for calculating all possible single hairpin loop secondary structures in a nucleic acid sequence by the order of N2 operations where N is the total number of bases. Each structure may contain any number of bulges and internal loops. Most natural sequences are found to be indistinguishable from random sequences in the potential of forming secondary structures, which is defined by the frequency of possible secondary structures calculated by the method. There is a strong correlation between the higher G+C content and the higher structure forming potential. Interestingly, the removal of intervening sequences in mRNAs is almost always accompanied by an increase in the G+C content, which may suggest an involvement of structural stabilization in the mRNA maturation.

Theory of sedimentation for ligand-mediated dimerization☆

Abstract The theory of sedimentation for ligand-mediated dimerization of a macromoleoule has been extended to take cognizance of the hydrodynamic dependence of the sedimentation coefficients of the reacting species upon concentration. The calculations are for rapid reequilibration during differential transport of macromonomer, dimer and ligand. For appropriate ratios of protein to ligand concentration the theoretical sedimentation patterns show bimodal reaction boundaries even when the concentration dependence of the sedimentation coefficients is severe. The boundaries are subject, however, to a Johnston-Ogston-type effect which accentuates the discrepancy between the relative areas of the two peaks and the relative, equilibrium concentrations of monomer and dimer. Nor do the peaks migrate with velocities per unit centrifugal field commensurate with the sedimentation coefficients of the monomer and dimer. Moreover, these quantities cannot be determined by extrapolation of the velocities of the peaks per unit field to infinite dilution of macromolecule at constant total ligand concentration.

THEORY OF SEDIMENTATION OF INTERACTING SYSTEMS

For some time we have been developing a computer code to predict the velocitysedimentation of systems of molecules that interact reversibly, and this will be a report of our progress. We are interested in exploring the consequences of the class of interactions in which a macromolecule, P, aggregates into an m-mer, with the mediation of a small molecule, HA, of which a fixed number, n, are bound into the complex. The reaction can be written: mP + nHA F? P,(HA),.

Bimodal Sedimenting Zones Due to Ligand-Mediated Interactions

Ligand-mediated association-dissociation reactions can give rise to band sedimentation patterns showing bimodal bands despite instantaneous establishment of equilibrium. Weaker interactions result in unimodal bands whose sedimentation coefficients decrease with time of sedimentation and in characteristic patterns of total ligand. The implications of these results for fundamental investigations of protein interactions and for conventional analytical applications of zone sedimentation and molecular sieve chromatography are considered.

A relational database system for the maintenance and verification of the Los Alamos sequence library

The nucleic acid sequence databases of Los Alamos National Laboratory, European Molecular Biology Laboratory, and others are organized in a single relational database. This organization with a suitable relational database management program facilitates the tasks of reporting statistics, making cross-references, and double-checking of the original databases.

TWO OR MORE ELECTROPHORETIC ZONES FROM A SINGLE MACROMOLECULE

Zone electrophoresis is a powerful method for separating macromolecules. Indeed, zone electrophoresis has found extensive application to the analysis of biological tissues and fluids, characterization of different molecular forms of enzymes and other biologically important macromolecules and their subunits, and to genetic analysis. In view of the great interest in these problems, a fundamental understanding of the electrophoretic transport of macromolecules which interact with each other, or with small molecules and ions, is imperative. Previously, the assumption often had been made that zone electrophoresis is immune to the several, nonideal effects which sometimes complicate moving-boundary electrophoresis. But, recent theoretical and experimental developments make it clear that the same caution must be exercised in interpreting zone-electrophoretic patterns as moving-boundary patterns.* In particular, cognizance must be taken of the fact that multiple zones need not necessarily indicate inherent heter0geneity.t As will be shown below, a single macromolecule interacting reversibly with a small, uncharged constituent of the solvent can give two zones despite instantaneous establishment of equilibrium. The situation can be even more complex. Thus, a single macromolecule, which isomerizes reversibly a t rates comparable to the rate of electrophoretic separation of the isomers, can give three zones. Furthermore, conclusions concerning the molecular nature of substances such a8 enzymes from zone electrophoresis on complex biological tissues and fluids such as serum, may be subject to considerable uncertainty, unless the possibility of interactions of macromolecules with each other is carefully elucidated. I t appears likely that multiplicity of zones due to interaction may be of more general occurrence than recognized. And, it is a disturbing fact that such patterns easily could be misinterpreted as indicating heterogeneity. However,

Products in the initial stages of digestion of polydeoxynucleotides by pancreatic deoxyribonuclease (DNase I).

Abstract Controlled partial digestion by pancreatic DNase (DNase I) of enzymically synthesized single-strand polydeoxynucleotides which contain short isotopically labeled segments at one or both ends of the chains has been carried out. Measurements have been made of the distribution of material and of radio-activity among the shortest oligomeric fragments. These data have been interpreted by calculating the expected values when assumptions are made concerning the rate of attack at each potentially hydrolyzable bond by the enzyme. It is inferred that the rate of attack on diester bonds within ten nucleotides of an end is much smaller than on bonds of the central region if the substrate molecule is several tens of nucleotides or less in length, but that this discrimination disappears as the substrate length increases.