1 4. Nucleic acids and proteins in one and more dimensions - second part

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mandatory to put some order in such a vast wealth of structural knowledge 4 4. Nucleic acids and proteins in one and more dimensions - second part

Taxonomy (from Ancient Greek: τάξις taxis, "arrangement," and -νομία -nomia, "method") is the science of defining groups of biological organisms on the basis of shared characteristics and giving names to those groups. Organisms are grouped together into taxa (singular: taxon) and given a taxonomic rank; groups of a given rank can be aggregated to form a super group of higher rank and thus create a taxonomic hierarchy Nucleic acids and proteins in one and more dimensions - second part Learning from Biology

4. Nucleic acids and proteins in one and more dimensions - second part 6 Learning from Biology

4. Nucleic acids and proteins in one and more dimensions - second part 7 protein structure taxonomy

8 4. Nucleic acids and proteins in one and more dimensions - second part protein structure taxonomy

9 4. Nucleic acids and proteins in one and more dimensions - second part protein structure taxonomy

10 4. Nucleic acids and proteins in one and more dimensions - second part protein structure taxonomy

11 4. Nucleic acids and proteins in one and more dimensions - second part protein structure taxonomy

12 4. Nucleic acids and proteins in one and more dimensions - second part protein structure taxonomy

13 4. Nucleic acids and proteins in one and more dimensions - second part protein structure taxonomy

red: mainly α green: mainly β yellow: αβ blue: low content of secondary structures Nucleic acids and proteins in one and more dimensions - second part protein structure taxonomy

15 4. Nucleic acids and proteins in one and more dimensions - second part protein structure taxonomy from most of different protein folds have been already found?

4. Nucleic acids and proteins in one and more dimensions - second part 16 comparing protein structure

4. Nucleic acids and proteins in one and more dimensions - second part 17 comparing protein structure

4. Nucleic acids and proteins in one and more dimensions - second part 18 comparing protein structure

4. Nucleic acids and proteins in one and more dimensions - second part proteins representative of the most common fold

4. Nucleic acids and proteins in one and more dimensions - second part 20

Structural genomics 0101# # # #10010#1001# # #0 DNA Algorithm Residue  THR THR CYS PRO Protein Structure X Ray diffractometry NMR cryo-electron tomography genome analysis

4. Nucleic acids and proteins in one and more dimensions - second part 22 from structural knowledge to structural predictions

secondary structure prediction Nucleic acids and proteins in one and more dimensions - second part

secondary structure prediction Nucleic acids and proteins in one and more dimensions - second part

CHOU & FASMAN Chou, P.Y. & Fasman, G.D. (1974). Biochemistry, 13, secondary structure prediction Nucleic acids and proteins in one and more dimensions - second part

secondary structure prediction # residues in window: Nucleic acids and proteins in one and more dimensions - second part

secondary structure prediction Nucleic acids and proteins in one and more dimensions - second part

secondary structure prediction Nucleic acids and proteins in one and more dimensions - second part

secondary structure prediction Nucleic acids and proteins in one and more dimensions - second part

secondary structure prediction Nucleic acids and proteins in one and more dimensions - second part

secondary structure prediction PSIPRED is a simple and reliable secondary structure prediction method, incorporating two feed- forward neural networks which perform an analysis on output obtained from PSI-BLAST (Position Specific Iterated - BLAST) Nucleic acids and proteins in one and more dimensions - second part

secondary structure prediction Nucleic acids and proteins in one and more dimensions - second part

secondary structure prediction Nucleic acids and proteins in one and more dimensions - second part

34 4. Nucleic acids and proteins in one and more dimensions - second part

Sequence Alignment “Two homologous sequences whisper... a full multiple alignment shouts out loud.” in Hubbard TJ, Lesk AM, Tramontano A. Gathering them in to the fold. Nat Struct Biol Apr;3(4):313.) Nucleic acids and proteins in one and more dimensions - second part

36 4. Nucleic acids and proteins in one and more dimensions - second part

37 4. Nucleic acids and proteins in one and more dimensions - second part

Letters corresponding to isolated matches are shown in non-bold type. The longest matching regions, shown in boldface, are the first and last names DOROTHY and HODGKIN. Shorter matching regions, such as the OTH of dorOTHy and crowfoOTHodgkin, or the RO of doROthy and cROwfoot, are noise. Dotplot showing identities between the palindromic sequence MAX I STAY AWAY AT SIX AM and itself. The palindrome reveals itself as a stretch of matches perpendicular to the main diagonal. Dotplot showing identities between a repetitive sequence (ABRACADABRACADABRA) and itself. The repeats appear on several subsidiary diagonals parallel to the main diagonal. From Introduction to Bioinformatics by Arthur M. Lesk dotplot The dotplot is a simple picture that gives an overview of the similarities between two sequences. Less obvious is its close relationship to alignments. The dotplot is a table or matrix. The rows correspond to the residues of one sequence and the columns to the residues of the other sequence. In its simplest form, the positions in the dotplot are left blank if the residues are different, and filled if they match. Stretches of similar residues show up as diagonals in the upper left-lower right (Northwest-Southeast) direction Nucleic acids and proteins in one and more dimensions - second part

39 4. Nucleic acids and proteins in one and more dimensions - second part

40 4. Nucleic acids and proteins in one and more dimensions - second part

BLOSUM62 matrix does an excellent job detecting similarities in distant sequences, and this is the matrix used by default in most recent alignment applications such as BLAST Nucleic acids and proteins in one and more dimensions - second part

Mutation probability matrix for the evolutionary distance of 250 PAMs Nucleic acids and proteins in one and more dimensions - second part

43 4. Nucleic acids and proteins in one and more dimensions - second part

44 4. Nucleic acids and proteins in one and more dimensions - second part

tertiary structure prediction Nucleic acids and proteins in one and more dimensions - second part

tertiary structure prediction Nucleic acids and proteins in one and more dimensions - second part

tertiary structure prediction Nucleic acids and proteins in one and more dimensions - second part

teminates with > Amino Acid Code Meaning A Alanine B Aspartic acidAspartic acid or AsparagineAsparagine C Cysteine D Aspartic acid E Glutamic acid F Phenylalanine G Glycine H Histidine I Isoleucine K Lysine L Leucine M Methionine N Asparagine O Pyrrolysine P Proline Q Glutamine R Arginine S Serine T Threonine U Selenocysteine V Valine W Tryptophan Y Tyrosine Z Glutamic acidGlutamic acid or GlutamineGlutamine X any * translation stop - gap of indeterminate length Nucleic acids and proteins in one and more dimensions - second part

49 4. Nucleic acids and proteins in one and more dimensions - second part

50 4. Nucleic acids and proteins in one and more dimensions - second part

tertiary structure prediction Nucleic acids and proteins in one and more dimensions - second part

tertiary structure prediction Nucleic acids and proteins in one and more dimensions - second part

tertiary structure prediction Nucleic acids and proteins in one and more dimensions - second part

Protein folding ab initio calculations of protein structure Nucleic acids and proteins in one and more dimensions - second part

MSSPQAPEDGQGCGDRGDPPGDLRSVLVTTV ROSETTA 9 aa fragments Selection of the closest 25 sequences Optimization and assembly (Knowledge-based potential) Protein fragments assembly Nucleic acids and proteins in one and more dimensions - second part

Rosetta Fragment Libraries fragments for each 3 and 9 residue sequence window Selected from database of known structures > 2.5Å resolution < 50% sequence identity Ranked by sequence similarity and similarity of predicted and known secondary structure Nucleic acids and proteins in one and more dimensions - second part

57 4. Nucleic acids and proteins in one and more dimensions - second part

58 RNA structure prediction

4. Nucleic acids and proteins in one and more dimensions - second part 59 RNA structure prediction Secondary structure of a telomerase RNA Primary structure of RNA Tertiary structure of RNA

4. Nucleic acids and proteins in one and more dimensions - second part 60 RNA structure prediction