1. Structures and Structure Descriptions Chapter 8 Protein Bioinformatics

2. Protein Classes 1.Active 1.Active – Mobility and catalysis –soluble and globular in shape 2.Passive 2.Passive – structural 3.Membrane 3.Membrane – control import and export through membrane

3. Folding in Globular Proteins fold into compact units 100-1000 nucleotides Stable fold has minimum energy –Native state Energy loss occurs when bonds are formed: –H-Bonds –disulfide bridges (cysteine) –metallic bonds w/ metal ions

4. Folding Formation of H-bonds: Hydrophilic amino acids are soluble, hydrophobic are not To maximize H-bonds, put hydrophilic on the surface so the whole protein is soluble Causes the formation of the two dominant Secondary Structure Elements (SSEs): 1.α-helix 2.β-strand

5. Structural Comparison Fine Level (residue) –used for finding spatial similarities – active and binding sites –helpful for determining function –done by specifying coordinates, distances, or torsion angles Coarse Level (SSE) –used for comparing on the global level –helpful for classifying proteins into classes –done by describing SSEs using line segments or as ellipsoids

6. Process

7. Structure Description ArchitectureArchitecture -position of (or Geometry) elements (atoms or residues) TopologyTopology -order of elements along the backbone PropertiesProperties -physio-chemical properties and types of SSEs

8. Coordinates From NMR or X-Ray Crystallography ATOM 1 N PRO A 2 31.242 3.064 39.284 1.00 39.90 N ATOM 2 CA PRO A 2 31.195 2.392 37.963 1.00 31.96 C ATOM 3 C PRO A 2 29.975 2.923 37.197 1.00 30.23 C ATOM 4 O PRO A 2 29.727 4.132 37.181 1.00 27.03 O ATOM 5 CB PRO A 2 31.063 0.905 38.251 1.00 36.57 C ATOM 6 CG PRO A 2 30.276 0.947 39.549 1.00 35.11 C ATOM 7 CD PRO A 2 30.829 2.121 40.343 1.00 42.06 C ATOM 8 N TYR A 3 29.189 2.020 36.613 1.00 22.83 N ATOM 9 CA TYR A 3 28.011 2.405 35.850 1.00 18.42 C ATOM 10 C TYR A 3 26.711 1.995 36.517 1.00 19.46 C ATOM 11 O TYR A 3 26.629 0.949 37.161 1.00 24.89 O ATOM 12 CB TYR A 3 28.055 1.772 34.459 1.00 17.73 C

9. Distance Matrices Distances can be stored with 3n-6 distances instead of 4n-10 coordinates. 2D representation of the 3D structure

10. Torsion Angles Angles between two bonds of each atom in the backbone are approx. equal Freedom comes in rotating around single bonds (-70,-20), (-72,60), (-70,120), (-60,170), (-65, 125), (-100, 45), (-100, -65), (-105, -66), (-100, 60)

11. Line Segments (sticks) Fit a line to the C  atom of each residue by least squares Ellipsoids Three inertial axes long axis corresponds to stick representation

12. Helices α-helix4-turn helix, min. 4 residues 3 10 -helix3-turn helix, min. 3 residues π-helix5-turn helix, min. 5 residues Formed by H- Bonds between residues in the same helix

13. Strands and Sheets Formed by successive H- Bonds between residues can be far apart in sequence.

14. Cartoons for Secondary Structure Elements (SSE) Topology of Protein Structure (TOPS) –Triangular symbols represent beta strands –Circular symbols represent helices (alpha and 310) –The peptide chain is divided into a number of fragments each labelled with an integer (i), beginning at Ni and ending at Ci+1. –The first fragment is N1->C2 (or N->C). –Each fragment lies in only one structural domain. –Where the chain crosses between domains it leaves the first at Ci and joins the next at Ni. –Each secondary structure element has a direction (N to C) which is either "up" ( out of the plane of the diagram ) or "down" (into the plane of the diagram).

15. Comparing Structures Structure Representations – pg. 185-186 (11-12 of pdf) –Strings –List of unit descriptions –Set of unit descriptions –Graphs –Feature Arrays

16. Pairwise Comparison Finding equivalence or alignment giving highest score is NP-Complete

18. Example Alignment –ACSL-DRTS-IRV –A-TLREKSSLIR- Know first 5 residues –ACSL-D –A-TLRE

19. But not so with structures Dynamic Programming cannot be used directly for structure alignment highest score alignment of entire structures highest score alignment of first five residues

20. RCSB PDB - HUMAN GLUTATHIONE S-TRANSFERASE Last Slide Explore pdb and install cn3d http://www.rcsb.org/pdbhttp://www.rcsb.org/pdb http://www.ncbi.nlm.nih.gov/Structure/ CN3D/cn3d.shtmlhttp://www.ncbi.nlm.nih.gov/Structure/ CN3D/cn3d.shtml