DNA, RNA, Protein Structure Prediction,Laura Pombo Laboratory of Computational Engineering Helsinki University of Technology,INTRODUCTION: Bioinformatics DNA RNA Proteins,BIOINFORMATICS,Bioinformatics involves the integration of computers, software tools, and databases in an effort to address biological questions. Bioinformatics approaches are often used for major initiatives that generate large data sets. Two important large-scale activities that use bioinformatics are genomics and proteomics. Genomics refers to the analysis of genomes. A genome can be thought of as the complete set of DNA sequences that codes for the hereditary material that is passed on from generation to generation. Thus, genomics refers to the sequencing and analysis of all of these genomic entities, including genes and transcripts, in an organism.,Bioinformatics, continue ,Proteomics, on the other hand, refers to the analysis of the complete set of proteins or proteome. In addition to genomics and proteomics, there are many more areas of biology where bioinformatics is being applied (i.e., metabolomics, transcriptomics). Each of these important areas in bioinformatics aims to understand complex biological systems. Many scientists today refer to the next wave in bioinformatics as systems biology, an approach to tackle new and complex biological questions. Systems biology involves the integration of genomics, proteomics, and bioinformatics information to create a whole system view of a biological entity.,Bioinformatics http:/www.bioinformatics.ubc.ca/,Central Dogma,DNA RNA Protein,DNA to RNA,Portions of DNA Sequence Are Transcribed into RNA The first step of a cell is to copy a particular portion of its DNA nucleotide sequence ( =gene) Similarities: DNA and RNA is a linear polymer made of four different types of nucleotide subunits linked together by phosphodiester bonds DNA and RNA contains the bases adenine (A), guanine (G) and cytosine (C) Differences: In RNA the nucleotides are ribonucleotides (=contain the sugar ribose) RNA contains uracil (U) instead of the thymine (T) My summary from the book: Molecular Biology of THE CELL (Bruce Alberts, et al.),Different RNAs,mRNAs (messenger RNAs), code for proteins rRNAs (ribosomal RNAs), form the basic structure of the ribosome and catalyze protein synthesis tRNAs (transfer RNA), central to protein synthesis as adaptors between mRNA and amino acids snRNAs (small nuclear RNAs), function in a variety of nuclear processes, including the splicing of pre-Mrna snoRNAs (small nucleolar RNAs), used to process and chemically modify rRNAs Other noncoding RNAs function in diverse cellular processes, including telomere synthesis, X-chromosome inactivation and the transport of proteins into te ER,RNA structure prediction,http:/gibk26.bse.kyutech.ac.jp/jouhou/image/dna-protein/all/N3utr.gif,RNA is transcribed (or synthesized) in cells as single strands of (ribose) nucleic acids. However, these sequences are not simply long strands of nucleotides. Rather, intra-strand base pairing will produce structures. In RNA, guanine and cytosine pair (GC) by forming a triple hydrogen bond, and adenine and uracil pair (AU) by a double hydrogen bond; additionally, guanine and uracil can form a single hydrogen bond base pair.,RNA structure prediction,Vienna RNA (PackageRNA Secondary Structure Prediction and Comparison) http:/www.tbi.univie.ac.at/ivo/RNA/ including a few precompiled binaries for download http:/www.tbi.univie.ac.at/ivo/RNA/windoze/ under Windows The Vienna RNA Package consists of a C code library and several stand-alone programs for the prediction and comparison of RNA secondary structures. RNA secondary structure prediction through energy minimization is the most used function in the package. The program provides three kinds of dynamic programming algorithms for structure prediction: the minimum free energy algorithm of (Zuker & Stiegler 1981) which yields a single optimal structure, the partition function algorithm of (McCaskill 1990) which calculates base pair probabilities in the thermodynamic ensemble, and the suboptimal folding algorithm of (Wuchty et.al 1999) which generates all suboptimal structures within a given energy range of the optimal energy.,RNAFOLD tool,RNAfold reads RNA sequences from stdin and calculates their minimum free energy (mfe) structure, partition function (pf) and base pairing probability matrix. It returns the mfe structure in bracket notation, its energy, the free energy of the thermodynamic ensemble and the frequency of the mfe structure in the ensemble to stdout. It also produces PostScript files with plots of the resulting secondary structure graph and a “dot plot“ of the base pairing matrix. The dot plot shows a matrix of squares with area proportional to the pairing probability in the upper half, and one square for each pair in the minimum free energy structure in the lower half,ALIDOT program,Detecting Conserved RNA Structures The program alidot