Structures and Structure Descriptions Chapter 8 Protein Bioinformatics

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

Folding in Globular Proteins fold into compact units 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

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

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

Process

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

Coordinates From NMR or X-Ray Crystallography ATOM 1 N PRO A N ATOM 2 CA PRO A C ATOM 3 C PRO A C ATOM 4 O PRO A O ATOM 5 CB PRO A C ATOM 6 CG PRO A C ATOM 7 CD PRO A C ATOM 8 N TYR A N ATOM 9 CA TYR A C ATOM 10 C TYR A C ATOM 11 O TYR A O ATOM 12 CB TYR A C

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

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)

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

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

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

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).

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

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

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

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

RCSB PDB - HUMAN GLUTATHIONE S-TRANSFERASE Last Slide Explore pdb and install cn3d CN3D/cn3d.shtmlhttp:// CN3D/cn3d.shtml