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

 Hydrogen Bonding  Intermolecular Forces  Dipole-Dipole  Ion-Dipole  Van der Waals

 Nonpolar molecules disrupt dynamic hydrogen bonds  Hydrophobic amino acids include  alanine, valine, leucine, isoleucine, phenylalanine, tryptophan and methionine

 Hydrophobic amino acids face the interior of the protein

 Hydrophobicity Scale  Physical scales based on surface tension or energy solvation  Wimley-White Scale  Peptide bonds and side chains  Experimentally determined values

 Refers to the total external charge, while polarity refers to the difference in charge

 Opposites attract, so charge can influence protein binding activity

 Physical structures resulting from amino acid sequences  Predictive techniques  FoldIt

 Binding sites  Chemical bonds from with ligands  Specific molecules and ions

 Critical Assessment of Protein Structure Prediction  Competition structure  Advancing predictive science  Based on structure, complex, domain, function

 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 data bank – PDB  Useful for low sequence similarity  Computational methods  X-Ray Crystallography  NMR Spectroscopy

 Distance alignment matrix based on hexapeptide contact patterns  FSSP (Families of Structurally Similar Proteins) Database  Server-based  DaliLite standalone

 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

 Sequential Structure Alignment Program  Vectors between non- contiguous residues  Optimal local alignments compiled into summary matrix  Dynamic programming

 Crystal  X-ray diffraction  Angles and intensities  Electron density  Atom positions and chemical bonds  Good resolution

 Water solution  Solid methods in development  Sample is placed in magnet  Different nuclei absorb different radio frequencies  Interaction  Determine orientation and structure