The sensitivity of the commonly used progressive multiple sequence alignment method has been greatly improved for the alignment of divergent protein sequences. Firstly, individual weights are assigned to each sequence in a partial alignment in order to down-weight near-duplicate sequences and up-weight the most divergent ones. Secondly, amino acid substitution matrices are varied at different alignment stages according to the divergence of the sequences to be aligned. Thirdly, residue-specific gap penalties and locally reduced gap penalties in hydrophilic regions encourage new gaps in potential loop regions rather than regular secondary structure. Fourthly, positions in early alignments where gaps have been opened receive locally reduced gap penalties to encourage the opening up of new gaps at these positions. These modifications are incorporated into a new program, CLUSTAL W which is freely available.

/pdf/clustal-w-improving-the-sensitivity-of-progressive-multiple-2na2s9sq2h.pdf

Clustal w: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice

The University of Wisconsin Genetics Computer Group (UWGCG) has been organized to develop computational tools for the analysis and publication of biological sequence data. A group of programs that will interact with each other has been developed for the Digital Equipment Corporation VAX computer using the VMS operating system. The programs available and the conditions for transfer are described.

/pdf/a-comprehensive-set-of-sequence-analysis-programs-for-the-luj6w12mfm.pdf

A comprehensive set of sequence analysis programs for the VAX

The abbreviated name,‘mfold web server’,describes a number of closely related software applications available on the World Wide Web (WWW) for the prediction of the secondary structure of single stranded nucleic acids. The objective of this web server is to provide easy access to RNA and DNA folding and hybridization software to the scientific community at large. By making use of universally available web GUIs (Graphical User Interfaces),the server circumvents the problem of portability of this software. Detailed output,in the form of structure plots with or without reliability information,single strand frequency plots and ‘energy dot plots’, are available for the folding of single sequences. A variety of ‘bulk’ servers give less information,but in a shorter time and for up to hundreds of sequences at once. The portal for the mfold web server is http://www.bioinfo.rpi.edu/applications/ mfold. This URL will be referred to as ‘MFOLDROOT’.

/pdf/mfold-web-server-for-nucleic-acid-folding-and-hybridization-3pzoe1h05m.pdf

Mfold web server for nucleic acid folding and hybridization prediction

https://njc.rockefeller.edu/pdf4/Class2-LeeAmbros1993.pdf

The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14

Subpopulations of RNA molecules that bind specifically to a variety of organic dyes have been isolated from a population of random sequence RNA molecules. Roughly one in 10(10) random sequence RNA molecules folds in such a way as to create a specific binding site for small ligands.

In vitro selection of RNA molecules that bind specific ligands.

Computerized sequence analysis is an integral part of biotechnological research, yet many biologists have received no formal training in this important technology. Sequence Analysis Primer offers the necessary background to enter this exploding field and helps more seasoned researchers to fine-tune their approach. Compatible with most sequence analysis programs, the primer covers basic data manipulation, and offers valuable advice for overcoming common problems. A detailed example giving steps for characterizing a new gene sequence provides users with "hands-on" experience when combined with their current software.

Sequence Analysis Primer

The codon preference plot is useful for locating genes in sequenced DNA, predicting the relative level of their expression and for detecting DNA sequencing errors resulting in the insertion or deletion of bases within a coding sequence. The three possible reading frames are displayed in parallel along with the open reading frames and plots of the location of rare codons in each reading frame.

The codon preference plot: graphic analysis of protein coding sequences and prediction of gene expression.

https://www.cell.com/cell/pdf/0092-8674(82)90465-2.pdf

Cloning and sequence analysis reveal structural variation among related zein genes in maize.

ilvIH of Escherichia coli K12 codes for a valine-sensitive acetohydroxy acid synthase (AHASIII). The DNA sequence of ilvIH was determined. Open reading frames and appropriate translation signals exist for two polypeptides, one containing 565 amino acids (ilvI polypeptide) and the other 160 amino acids (ilvH polypeptide). A graphic matrix analysis shows three clearcut regions of homology between ilvI and ilvG (codes for AHASII). Within these three regions of homology, 50-60% of the amino acid sequences of AHASII and AHASIII are conserved. Inspection of the region between ilvG and ilvE (the K region) revealed that it can potentially code for an 86 amino acid polypeptide. A computer analysis shows small but significant homology between the predicted amino acid sequences of the N-terminal half of the ilvH polypeptide and the putative region K polypeptide. We conclude that ilvIH and ilvG-region K evolved from a common ancestor.

John Devereux

Papers

A comprehensive set of sequence analysis programs for the VAX

Sequence Analysis Primer

The codon preference plot: graphic analysis of protein coding sequences and prediction of gene expression.

Cloning and sequence analysis reveal structural variation among related zein genes in maize.

Molecular structure of ilvIH and its evolutionary relationship to ilvG in Escherichia coli K12