Proteins

Proteins

1. 4 levels of protein structure

   • 3D Structures
     • Reason for folding
       • Increase in Gibbs
         • Folded protein are only marginally more stable than unfolded form. Although unfolded = high entropy, the increase in enthalpy (in folded protein) due to the many weak, noncovalent interactions, dominatie
       • 2nd Law thermodynamics - burial of hydrophobic residues
         • Entropy of solvent INCREASES, thus outweighing the decreased entropy of protein
           • Unfolded protein: H2O forms hydration spheres around hydrophobic sidechains
           • Fold proteins: hydrophobic residues become buried in interior part of protein, so hydration spheres no longer needed.
     • How proteins fold
       • Afinsen Paradigm
         • The 3D structure of a protein is entirely determined by its amino acid sequence
   • Secondary Structure
     • Most stable protein folds = maximised hydrogen bond formation
       • Alpha Helices
         • Polypeptide backbone folded so that the C=O group of residue i is hydrogen bonded to NH group of residue i+4
         • L-amino acids: Right handed helices favoured
         • a helices do not have hollow centres
         • Have dipoles
       • Beta Sheets
         • Driven by interstrand H-bonds
         • Parallel B Sheets
           • Diagonal bonds, evenly spaced
         • Antiparallel B sheets
           • Straight H bonds, unevenly spaced
         • Side chains alternate above and below
         • Pleated
         • Less tolerant of large side chains than a helices
         • B sheet can have mix parallel and anti
           • Beta barrel
       • Hydrogen Bonding
   • Primary Structure
     • Amino Acids
     • Peptide Bonds
       • Peptide bond Resonance
         • Peptide bond length is closer to double bond than single.
           • Peptide bond: inflexible and planar Backbone bonds can rotate freely
     • Describing protein structure
       • Backbone conformation described by: ωφψ Side chain: Χ
       • x,y,z coordinates for atoms
     • Restriction on conformation in space
       • Trans, more stable than cis (accept X-Pro)
       • Ramachandran Principle
       • Most sidechains adopt 1/3 staggered conformations

2. Representation Protein Structure

   • Richardson Representations
     • a helices ribbons/cylinders B strands arrows (N->C) other: string
   • CPK Models
     • Each atom represented as sphere with radius ~ to atom's VDW radius
   • Molecular surface Representions
     • Solvent-accessible surface
     • Solvent-excluded surface / Connelly surface
       • Visualise crevices and bumps. Also, charge distribution (colours)
   • Wireframe
     • Connecting bonds
   • Ball and stick
     • Bonds = tubes atoms = ball smaller than vDW r
   • aC trace
     • Virtual bonds between aC
   • Backbone trace
     • aC, N, Carbonyl joined by actual bonds
   • Divergent stereoviews

3. Domains

   • Conserved protein sequence/tertiary structure than can function independently of the rest of protein chain
   • Intradomain interactions > interdomain

Images and files in the map