AMINO ACIDS AND PROTEIN STRUCTURE
Feb 24, 2016
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