MEDCHEM E CHEMBIO Lecture 6 Bond Types / interactions

• Covalent bonding


  Bond that involves the sharing of electron pairs between atoms
• Non-covalent bonding


  Examples: Hydrogen bonding, Ionic bonding
• Hydrogen bonds are very common in proteins
• Secondary structure of a protein

  • 3D form of local segments of proteins, i.e. a-helices, b-sheet, loops
  • Involves interactions (mainly hydrogen bonds) between neighboring polypeptide backbones
  • Though they are relatively weak, these bonds offer great stability to secondary protein structure because they repeat a great number of times
• Van der Waals forces

  Attraction between two oppositely oriented transient dipoles in nearby molecules
• One way to think about molecules (neutral) is to consider them as a collection of nuclei surrounded by a "cloud" of electrons
• The electrons within this cloud are always moving. Sometimes one area of the cloud is more dense than another, leading to the formation of a transient dipole within the molecule
• The transient dipole can induce a dipole in a nearby molecule, by attracting its electrons

  
• Van der Waals forces

  Electrostatic interactions, particularly important in biomolecules
• Hydrophobic interactions


  Effective interaction between two non-polar molecules that tend to avoid water and prefer to cluster around each other
• Hydrophobic interactions


  • Important for the folding of proteins
  • As a protein folds, amino acids with hydrophobic side chains are packed inside the structure, away from the surrounding water molecules
• Salt bridges


  Bonds between oppositely charged residues that are sufficiently close to each other to experience electrostatic attraction, often between carboxylate of aspartic/glutamic acid and ammonium of lysine/guanidinium of arginine
• Aromatic-aromatic interactions


  Attractive, non-covalent interactions between aromatic rings, where the π face of one ring interacts with the partially positively charged hydrogen atoms on the edge of another ring
• The most stable geometry for aromatic-aromatic interactions is either parallel-displaced or T-shaped, while the sandwich configuration is least stable
• Cation-π interactions


  Positively charged species (cations) are attracted to the regions of p-electron density above and below the plane of an aromatic ring
• In proteins, the aromatic amino acids phenylalanine, tyrosine, and tryptophan are very effective at stabilizing positively charged reaction substrates or intermediates (or inhibitors!) that are bound deep in the hydrophobic core of the enzyme