Four levels of protein structure Linear Sub-Structure 3D Structure Complex Structure

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