04 Noncovalent Interactions - Non-Covalent Interactions...

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Unformatted text preview: Non-Covalent Interactions Core Learning Goal: – Understand the Relationship between Macromolecular structure and function: • The physical basis of interactions • Thermodynamics of macromolecular structure formation Learning Objectives: • Identify Hydrogen bonds and the functional groups that can form them. • Compare and contrast the nature of non-covalent interactions – Rank them by strength and be able to justify this ranking. • Discuss how the physical characteristics of water affect biological molecules. • Explain the similarities between macromolecules with respect to: – Structure formation. – Structural diversity Importance of Water • Physical and Chemical properties of water influence every biochemical interaction. – the medium for most biochemical reactions – participates in many biochemical reactions – Affects folding (structure) of biomolecules Physical Properties of Water: Structure of A Water Molecule hydrogens have a partial positive charge; oxygen has partial negative charge Water is a Polar Molecule: Permanent Dipole (Electronegativity of Oxygen) δ- δ+ H 2e– O 2e– Figure 2-1a H Hydrogen Bonding attraction between a partially charged hydrogen and the lone pair on an electronegative atom δ+ δ- donator acceptor Figure 2-2 Characteristics of Hydrogen Bonds • Length = 1.8Å (versus 0.96 Å) • Strength ≈20kJ/mol (versus 460kJ/mol) • Most stable when linear Example of Weak Interaction Urea is a water-soluble product of nitrogen metabolism. How many hydrogen bonds can one urea molecule donate to surrounding water molecules? A) B) C) D) E) 2 3 4 5 6 Is this a hydrogen bond? A. Yes B. No Is this a hydrogen bond? A. Yes B. No Effect of Water on the Structure of Biomolecules: Depends on Physical Characteristics: Charged Polar Non-Polar Solvation of Ions water can solvate water: partial negative charges on oxygen can surround a positive ion and the partial positive charges on hydrogen can surround a negative ion Figure 2-6 Hydrogen Bonding by Functional Groups Figure 2-7 Orientation of Water Molecules Around a Nonpolar Solute if you put a nonpolar solute into water, the hydrogens of water cannot form hydrogen bonds with the nonpolar molecule (because it is hydrophobic) so they are trapped in highly ordered water cages entropically unfavorable water cages surround nonpolar molecules, nonpolar molecules aggregate together and this minimizes the surface area of the nonpolar molecules and decreases the number of water molecules that are trapped in the cages and the entropy of the water of the surrounding solvent increased entropy Aggregation of Nonpolar Molecules in Water water cages released = entropy increase; nonpolar inside, polar on surface water is interacting with the hydrophopic region of fatty acid; interaction breaks in order for fatty acid to form micelle, Which of the following is true regarding the hydrophobic effect? A. Nonpolar molecules interrupt the hydrogen-bonding pattern of water B. Association of hydrophobic compounds with each other increases the entropy of water C. Hydrophobic aggregation is thermodynamically favorable due to the hydrophobic interactions formed. D. A and B E. All of the above hydrophobic aggregation is thermodynamically favorable due to the increase in entropy of water Intermolecular Interactions inter - between two different molecules; intra- within a single molecule S—S van der waals = any noncovalent interaction that does not involve full charges Table 2-1 all have partial charges that create an attractive force van der Waals Interactions smaller partial charges so weaker interactions induced dipole-induced dipole attraction Figure 2-5 larger partial charges so stronger interactions dipole induces a dipole on a functional group that is not polar hydrophobic interactions Which of the following statements is FALSE regarding London Dispersion forces? A. They are formed between non-polar functional groups. B. They form by functional groups being pushed away from water. C. They involve an attractive force between opposite charges. D. They are responsible for holding macromolecules together. they are WEAK; BUT there is so many of them that they play a role in holding the protein together Protein Folding How proteins find their native structure ribosome translate mRNA into polypeptide and then it folds into tertiary structure (most stable structure/native conformation) mRNA ribosome nascent polypeptide folding Folded polypeptide What Drives Protein Folding? polar amino acids can form hydrogen bonds with water in the unfolded state and can fold hydrogen bonds with water OR with each other in the folded state: so change in enthalpy is 0/close to 0 because the energy is lost when breaking a hydrogen bond but then a new hydrogen bond is formed Proteins try to reach the conformation with lowest free energy - Driven by Hydrophobic effect and Stabilized by formation of weak interactions nonpolar amino acids form an induced dipole interaction with water in unfolded form and can form induced dipole interactions with water and with each other in the folded form so delta H = 0 Non-Polar residue Induced Dipoles hydrophobic molecules in polypeptide trap water into amino acid Polar residue delta S = positive which causes a negative delta G (FAVORABLE!!) H-bonds increase in entropy of water: hydrophobic molecules cause water to form cages around them, when protein folds hydrophoic molecules go into center and water is broken from cages; change in enthalpy looks at strength at bonds in folded vs unfolded state, anything present in the unfolded state has to be broken (energy lost) anything in the folded state has to be formed (energy created) Water is highly ordered Water has higher disorder Protein Folding Pathway Folding Funnels as it goes through this process, there are fewer possible confirmations proteins can make large degree of entropy in folded state Secondary structure (ms-s) Hydrophobic collapse (ms) hydrophobic amino acids forming core of protein Tertiary structure new hydrophillic amino acids are (s) now next to each other after hydrophilic collapse; trying to find lowest energy native structure = ONLY 1 forming the most possible weak interactions within that polypeptide; lowest energy Protein Stability: Depends on strength of weak interactions and how many are present can measure stability of protein by how much energy is required to unfold/ denature that protein • Denaturation by: – Heat – Change in pH – Urea or Guanidinium • Mutations can affect the stability of a protein. – A4V mutation in SOD linked to ALS Tm = temperature where 50% of protein has denatured; known as melting temp. higher melting temperature = more energy to denature protein (so more stable protein) Protein folding is: I. Enthalpically driven II. Entropically driven III. Enthalpically favorable IV. Entropically favorable A. I, III B. II, IV C. I, III, IV D. II, III, IV In Vitro vs. in Vivo Folding • in vivo, protein folding is usually highly efficient (E. coli: 100 AA protein / 5 s) • in vitro, protein folding is often problematic and very inefficient • biggest problem: Protein aggregation protein is nonfunctional when aggregated proteins come offf ribosome in unfolded state; many can fold on their own; those that take awhile may have hydrophobic regions exposed and will find another protein to aggregate with and cover those hydrophobic regions In vivo: Molecular Chaperones Molecular Chaperones Prevent Protein Aggregation proteins that can bind to unfolded proteins and shield them from aggregation to give them enough time to fold and then the chaperone will be released Unfolded nascent polypeptide molecular chaperone chaperone recognizes unfolded protein by hydrophobic regions aggregates U1 + chaperone Folded Protein Misfolding Diseases aggregate does not form disease but related Table 6-4 Macromolecular Structure Formation • Driven by the hydrophobic effect • Stabilized by non-covalent interactions • Simple building blocks combined differently for structural diversity • • • • DNA helix formation Protein Folding Membrane Formation Polysaccharide structure all find native structures through same process Principle of Structural Simplicity with increasing diversity: Polymerization Precursors (few) Polymerization H2O Macromolecules (many) [Polymers] Biological Macromolecules a few different precursers that we have to know how to make and string them together in different ways and can make 100 of thousands of different proteins Nucleic Acids Proteins Carbohydrates (Lipids) all polymers (except lipids) increase in diversity and complexity from bacteria to us was possible because all of these are polymers; dont have to make a different molecule; still same 20 amino acids just strung together in different ways Biopolymers Homopolymer Linear Heteropolymer all of the individual residues are the same precursor any 1 residue is a different amino acid Branched Nucleic Acids (Nucleotides) NH2 N N O O O P O O P O O O NH2 N O CH2 P O O O O P O OH OH Ribonucleotides O O P O O O P O O O O P O O P O CH2 O N O OH P N N O CH2 O O O P O OH P O OH O CH2 Nucleic Acids N O O O O OH O P O O O O O O N O N N N N 4 Nucleotides O OH OH Only linear structures Dinucleotide N1–N2–N3–…Nn Number of structures = 4n 1,000,000 nucleotides per DNA molecule 41,000,000 molecules!!! Proteins (Amino Acids) Only 20 naturally-occurring amino acids Only linear structures aa1–aa2–aa3–…aan Number of structures = 20n If only 100 amino acids per molecule 20100 molecules different molecules possible Polysaccharides (Sugars) Only a few sugars (~8) Linear and branched molecules Homopolymers and Heteropolymers Lipids (Various Precursors) Phospholipids At least 2 different backbones At least 12 different fatty acids Up to 7 different R3 substituents, or saccharides Simple construction provides an immense number of possible structures fully capable of providing the necessary diversity required for life. ...
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