The presence of adenosine (red) between the two stems of a pseudoknot creates a bend in the pseudoknots's shape that helps the retrovirus to reproduce.

"in silico DNA, RNA, Protein Sequence,
and Structure Analysis:

Theory and Practice"

Thursday, 9 January 1997

Morning Lectures

9:30 AM Role of Theory: "I would not have seen it if I had not believed it."

"Topology of DNA: Knots No Sailor Ever Knew"

How does all that chromosomal DNA fit into a 1 micron cubed space of a bacterial cell without being a knotted tangle? What is a coiled coiled coiled coil structure of DNA in an eucaryotic chromosome? How do topisomerases, helicases, and recombinases work? Links, writhes, twists, and concatenanes will be introduced in such a fashion that will help you look at electron micrographs of DNA or electrophoretograms of supercoiled DNA with understanding. Hence, we can appreciate the theoretician's ironic maxim: "I wouldn't have seen it, if I had not believed it."


10:45 AM Break

11:15 AM RNA Secondary Structure: Hairpins ("Airports"), Nussinov Circles, Reinhardt Domes, Mountains, Pseudo Knots and Computational Problems; Multiple Approaches to a Single Problem: Thermodynamics, Enzymology, Phylogeny, Information Theory; Electrophoresis; etc.

"RNA Secondary Structure: A Multidisciplinary Structure "

Modelling can be informed by multiple perspectives. The folding of biological macromolecules is an exceptionally difficult problem that is especially informed by evolutionary homology of conserved regions, by ab initio calculations based upon thermodynamic parameters and statistical mechanical modelling approaches, by biophysical measurements (X-ray crystallography, NMR spectroscopy, scanning tunnel electron microscopy, electrophoresis, sedimentation), by in vivo and in vitro biochemical studies (sites of RNA or DNA lysis or proteolysis), by thermodynamic measurements per se, and by aesthetic considerations. We will argue that unless a secondary structure is examined from at least several of these perspectives, it is highly unlikely (given the combinatorial explosion by potential conformers) that a reported single secondary structure is believable. In addition, multiple approaching towards viewing RNA secondary structure will be explained: squiggles (airports), mountains, domes, and Nussinov circles. Also, this problem will help biologists understand why the power of supercomputers such as the Cray at HPCC are highly desireable for biological problems.


12:30PM - 2PM Lunch

Afternoon Laboratories

2-3:30 PM AM RNA Secondary Structure. Molecular Graphics: drawing packages, various molecular viewng packages,etc.
SOFTWARE: NCBI (web), RNADraw (Win), Mfold (Web), Mulfold2 (MacOS, Unix), LoopDLoop (MacOS), and DottyPlot (Mac)

3:30 PM Break

3:45 - 5 PM Continuation of the early afternoon session expanded to include other programs that do similiar things.

SOFTWARE: Kinemages (MacOS, Windows, Unix) viewing PDB files, PDBBrowse (web), and FoldIt Light (MacOS) or MacMolecule (MacOS) molecular modeling programs.



Description: A Windows tool for folding and drawing RNA secondary structures. It can also take structures folded with Zuker's mfold and display them.

Written by: Ole Matzura (University Sweeden)

For more information: RNADraw Homepage

Mulfold & Mulfold2

Description: RNA folding program. Two different versions exist- Mulfold2 is written in fortran for running under UNIX. Don Gilbert added a Macintosh front end and now simple (<300 bp) calculations can be run on your own computer.

Written by: Michael Zuker, John Jaeger (Washington University in St. Louis) & Don Gilbert (Indiana University)

For more information: Mulfold readme


Description: A Macintosh tool for drawing RNA secondary structures. NOTE: it does NOT an RNA folding program. It accepts input from several different programs. A Java form of the program is in its initial alpha testing! Hopefully it will be ready SOON!.

Written by: Don Gilbert (Indiana University)

For more information: loopDloop readme


Description: A Macintosh tool for drawing dot matrix comparisons of sequences in molecular biology.

Written by: Don Gilbert (Indiana University)

For more information: DottyPlot readme

Kinemages (MAGE)

Description: A 'kinemage' [kinetic image] is a scientific illustration presented as an interactive computer display. The entire image can be rotated in real time, parts of the display can be turned on or off, any point can be identified by picking it, and the change between different forms can be aninmated. Kinemages are created from Brookhaven Protein Data Bank files using the program PREKIN. The MAGE programs run under MS-Windows, Macintosh and UNIX operating systems.

Written by: David Richardson (Duke University)

For more information: MAGE readme

FoldIt Light

Description: A Macintosh only program to visualize and manipulate proteins with a user friendly interface. The goal of this program was to build an integrated environment in which statistical analysis as well 3D observations could be realized on PDB files without having to transfer files or swap machines.

Written by: Jean-Claude Jesior (IMAG, France)

MacMolecule2 Lite

Description: A Macintosh only program to render and visualize proteins with a user friendly interface.

Written by: S. Selznick, E. Myers, R. Hallick (Univ. of Arizona)

For more information: MacMolecule Homepage


NCBI (Genbank) Text Searching

M. Zuker's RNA page and link to his web RNA folder

PDB 3DB Browser

Handy biological software:

IUBio Software

Pedro's BioMolecular Research Tools

Bibliography - Topology of DNA: Knots No Sailor Ever Knew

Simmons, Henry. 198. "DNA Topology: Knots No Sailor Ever Knew." Mosaic 2(1):2-10 (January/February).

Scovell, William M. 1986. "Supercoiled DNA." J. Chemical Education 63(7):562-565.

Dazey, Isabel K., Spengler, Sylvia J. and Sumners, De Witt. Department of Mathematics, Florida State University, Tallahassee, FL USA.

V‡zquez, Ma. Elena, Dazey, Isabel, and Sumners, De Witt. "Tangle Analysis of Processive Gin Recombination." Department of Mathematics, Florida State University, Tallahassee, FL USA


Bibliography - RNA Secondary Structure: A Multidisciplinary Structure

Westhof, Eric, and Michel, Franois. 1994. "Prediction and experimental investigation of RNA secondary and tertiary foldings." Pp. 25-50in Nagai, Kiyoshi and Iain Mattaj, Eds. RNA-Protein Interactions. Oxford University Press.

Zuker, Michael. 1995. "Prediction of RNA Secondary Structure." WEB Page.

Springer, M. S. and E. Douzzery. 1996. "Secondary Structure and Patterns of Evolution Among Mammalian Mitochondrial 2S rRNA Molecules," J. Mol. Evol. 43:357-373.

deLannoy, Peter, Easterwood,, LaHoma, Bynote, Kimberly, and Smith, Stanley. 1996. "Structure Leads to Function: An Integrated Biophysical Approach to Teaching a Biochemistry Laboratory." Bioscene 22(3):3-9 (December).

SŸhnel, J. 1996. "The RNA World." IMB Jena, Biocomputing, POB 100 813, D-07708 Jena.

Hofacker, Ivo. 1996. "Vienna RNA Package." Institut fŸr theoretische Chemie, WŠhringerstr. 17, A-1090 Wien, Austria.

Steger, G., Hofman, H., Foertsch, H., Gross, H. J., Ranndles, J. W., Saenger, H. L. and Riesner, D. 1984. Conformational Transitions in Viroids and Virusoids: Comparison of results from energy minimisation algorithm and from experimental data. J. Biomol. Struct. Dyn. 2:543-571.

Schmitz, M. & Steger, G. 1992. Base-pair probability profiles of RNA secondary structures. Comput. Appl. Biosci. 8:389-399.

Mangalam, Harry. 1996. "Sequence to Structure." WEB Page

Kobayashi, Satoshi and Yokomori, Takashi. 1996. "Modeling RNA Secondary Structures Using Tree Grammars." WEB Page. Department of Computer Science and Information Mathematics, The University of Electro-Communications, 1-5-1, Chofugaoka, Chofu, Tokyo 182, Japan.

Uemura, Yasuao, Hasegawa, Aki, Kobayashi, Satoshi and Yokomori, Takashi. 1996. "Grammatically Modeling and Predicting RNA Secondary Structures." WEB Page. Department of Computer Science and Information Mathematics, The University of Electro-Communications, 1-5-1, Chofugaoka, Chofu, Tokyo 182, Japan.

Winnepenninckx, Birgitta, Van de Peer, Yves, Backeljau, Thierry and De Wachter, Rupert. 1993. "CARD: A computer program for drawing RNA secondary structure models." WEB Page. Department of Biochemistry, University of Antwerp (UIA), Universiteitsplein 1, 2610, Wilrijk-Antwerpen, Belgium.

Huynen, Martijn. "Analyzing the base pair probability distribution of large RNA molecules." Theoretical Biology and Biophysics and Center for Non Linear Studies MS B258, Los Alamos National Laboratory, Los Alamos, NM 87545.


Last modified: Wed Jan 1 14:56:25 1997