AMINO ACIDS AND PROTEIN STRUCTURE
PROTEIN STRUCTURE
Four levels of protein structure Linear Sub-Structure 3D Structure Complex Structure
POLARITY
Hydrogen Bonding Intermolecular
Forces Dipole-Dipole Ion-Dipole Van der Waals
HYDROPHOBIC EFFECT
Nonpolar molecules disrupt dynamic hydrogen bonds
Hydrophobic amino acids include alanine, valine,
leucine, isoleucine, phenylalanine, tryptophan and methionine
HYDROPHOBICITY IN PROTEIN FOLDING Hydrophobic amino
acids face the interior of the protein
HYDROPHOBICITY NUMBER
Hydrophobicity Scale Physical scales
based on surface tension or energy solvation
Wimley-White Scale Peptide bonds and
side chains Experimentally
determined values
CHARGE
Refers to the total external charge, while polarity refers to the difference in charge
CHARGE IN PROTEIN INTERACTIONS
Opposites attract, so charge can influence protein binding activity
AMINO ACID SIZE
SUMMARY
PROTEIN FOLDING
Physical structures resulting from amino acid sequences
Predictive techniques FoldIt
INTERACTION
Binding sites Chemical bonds from with ligands Specific molecules and ions
CASP
Critical Assessment of Protein Structure Prediction Competition structure Advancing predictive science Based on structure, complex, domain, function
SCOP
Structural Classification of Proteins
Collaborative classification effort
Based on amino acid sequence, domain structure, and function
Classified into families and superfamilies
Sourced from Protein Data Bank (PDB)
PROTEIN STRUCTURE ALIGNMENT
Protein data bank – PDB Useful for low sequence similarity Computational methods X-Ray Crystallography NMR Spectroscopy
DALI
Distance alignment matrix based on hexapeptide contact patterns
FSSP (Families of Structurally Similar Proteins) Database
Server-based DaliLite standalone
COMBINATORIAL EXTENSION
Breaks structures into aligned fragment pairs
Originally only structural superpositions and inter-residue distances
Now includes secondary structure, solvent exposure, hydrogen-bonding patterns, and dihedral angles
SSAP
Sequential Structure Alignment Program
Vectors between non-contiguous residues
Optimal local alignments compiled into summary matrix
Dynamic programming
X-RAY CRYSTALLOGRAPHY
Crystal X-ray diffraction Angles and
intensities Electron density Atom positions and
chemical bonds Good resolution
NUCLEAR MAGNETIC RESONANCE (NMR) Water solution Solid methods in
development Sample is placed in
magnet Different nuclei
absorb different radio frequencies
Interaction Determine orientation
and structure