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