This is version 2 of Michael Zuker's Suboptimal RNA Folding package. The files are a combination of those I received directly from Dr. Zuker when the package was at version 1. The version 2 files were obtained via anonymous ftp from Don Gilbert's ftp.bio.indiana.edu archive. I have also added a couple DCL scripts used to setup the MFOLD environment. If your ftp package does VMS Structure transfers then you just need to get the MFOLD.BCK file. If you do not have the VMS Structure feature then you MUST transfer MFOLD.BCK in binary mode. Then transfer FIXREC.EXE as binary, and use FIXREC to fix the block size of the MFOLD.BCK file before VMS BACKUP will be able to read the file correctly. ----- READ_ME.FIRST from Zuker and Jaeger ------------------------------------ MFOLD - Prediction of RNA secondary structure by free energy minimization. - Version 2.0 - Michael Zuker and John Jaeger - LRNA : folds linear RNA sequences - CRNA : folds circular RNA sequences The original version (1.0) was designed by Michael Zuker and programmed by Eric Nelson in the summer of 1987 in the Division of Biological Sciences at the National Research Council of Canada. John Jaeger added the tetraloop bonus energy feature and created the BATGEN program for batch file generation. Version 2.0 corrects a number of small bugs from the original program. These were added to version 1 and itemized in the ERRATA.LIST file that was distributed along with version 1. The major improvements of version 2 are : 1. During the generation of suboptimal foldings, the number of new base pairs that are sufficiently different from base pairs that have already been found must be greater than the WINDOW parameter. This feature was added during the summer of 1989, and was made part of version 1 (item 11 in the ERRATA.LIST file distributed with this version). The effect is to eliminate structures that contain just a few new base pairs. 2. Temperature dependent folding. This was added in the fall of 1989 and was never a feature of version 1. 3. The multiple sequence option will now generate suboptimal foldings of all the sequences in an input file. This can be used (for example), to compute all foldings within 10% of the minimum energy for all the 5S RNAs conained in a single file. METHOD : A dynamic programming algorithm is used to find optimal and suboptimal foldings of an RNA molecule starting from linear sequence data. Auxiliary information can be used to constrain the folding. Energy data from : S.M. Freier et al., Proc. Natl. Acad. Sci. USA, 83, 9373-9377, 1986. D.H. Turner et al., Cold Spring Harbor Symposia on Quantitative Biology, 52, 123-133, 1987. D.H. Turner et al., Annu. Rev. Biophys. Biophys. Chem 17, 167-192 (1988). This last reference has all the dangling end and terminal mismatch data. References : M. Zuker On Finding All Suboptimal Foldings of an RNA Molecule. Science, 244, 48-52, (1989) J. A. Jaeger, D. H. Turner and M. Zuker Improved Predictions of Secondary Structures for RNA. Proc. Natl. Acad. Sci. USA, BIOCHEMISTRY, 86, 7706-7710, (1989) J. A. Jaeger, D. H. Turner and M. Zuker Predicting Optimal and Suboptimal Secondary Structure for RNA. in "Molecular Evolution: Computer Analysis of Protein and Nucleic Acid Sequences", R. F. Doolittle ed. Methods in Enzymology, 183, 281-306 (1989) see also: M. Zuker Computer Prediction of RNA Structure. in "RNA Processing", J. E. Dahlberg and J. N. Abelson eds. Methods in Enzymology, 180, 262-288, (1989) M. Zuker The Use of Dynamic Programming Algorithms in RNA Secondary Structure Prediction. in "Mathematical Methods for DNA Sequences", M. S. Waterman ed. CRC Press, Inc., 159-184, (1989) A.B. Jacobson, M. Zuker and A. Hirashima Comparitive Studies on the Secondary Structure of the RNAs of Related RNA Coliphages. in "Molecular Biology of RNA: New Perspectives", M. Inouye and B. S. Dudock eds. Academic Press, Inc., 331-354, (1987) Use : LRNA and CRNA are ready to use. They can be run by issuing the commands : $ Run LRNA or $ Run CRNA You must execute the command file INIT.COM before attempting any run with energy dot plots. The files LIN.COM and CIRC.COM are command files that compile and link LRNA and CRNA respectively. These files should be copied into the temporary file TEMP.COM. TEMP.COM can then be edited to remove redundant compilations. The dimensions can be altered by changing LIN.INC (linear RNA folding) or CIRC.INC (circular RNA folding). If LIN.INC or CIRC.INC is changed, then ALL subroutines used by LRNA or CRNA must be recompiled with the exception of FORMID and MULTID. FILES.LIST contains a list and description of all files used for folding. Note the sample runs of the ALU sequence and the batch files (BAT1.COM and BAT2.COM that produced them). MFOLD.USER is a user's manual. MFOLD.DOC is a glossary of functions, subroutines and variables. MFOLD.FLOW is a crude flow chart of the MAIN program of MFOLD.