Biochem midterm 1

What are the five main types of non-covalent interactions covered in Lecture 2?

Hydrogen bonds, electrostatic/ionic interactions (salt bridges), van der Waals interactions, aromatic (pi-stacking) interactions, and the hydrophobic effect.

What is a dipole?

A separation of positive and negative charge within a molecule or bond.

What is the formula for dipole moment, and what does each term mean?

mu = q x r, where q = magnitude of charge and r = distance between the charges (units: Debye, or Coulomb-meters).

What makes a covalent bond polarized?

One atom (the more electronegative one) draws electron density toward itself, creating partial positive and negative charges (delta+ / delta-).

What is the optimal hydrogen bond distance?

2.4 to 2.7 Angstroms.

In a hydrogen bond, what is the 'donor'?

The atom bearing the H that is being shared/donated (e.g., the N or O attached to that H); the donor H has a partial positive charge from being attached to an electronegative atom.

Why does the angle of a hydrogen bond matter?

H-bond strength is maximal at 180 degrees (linear); as the angle deviates from linear, the H-bond becomes weaker.

What is the van der Waals radius (r_vdw)?

Half the distance of closest approach between two non-bonded atoms of a given element; atoms interact optimally when the distance between them equals the sum of their van der Waals radii.

What are the three types of van der Waals interactions?

(1) dipole-dipole, (2) dipole-induced dipole, (3) induced dipole-induced dipole (London dispersion forces).

What causes van der Waals / London dispersion forces?

Transient fluctuations in electron clouds create temporary dipoles that mutually reinforce (induce) dipoles in neighboring atoms.

What creates 'steric effects' at short interatomic distances?

Electron cloud repulsion when atoms get closer than their combined van der Waals radii; this repulsion constrains 3D biomolecular structure.

What is Coulomb's Law, and what does it describe?

V(r) = (1/4piepsilon) x (q1*q2 / r); it describes the potential energy of an electrostatic (ionic) interaction between two charges, where epsilon is the electric permittivity of the medium.

What are the relative permittivity (dielectric constant) values for vacuum, water, and a cell membrane/protein interior?

Vacuum: epsilon_r = 1; Water: epsilon_r = 80; Cell membrane/protein interior: epsilon_r = 2 to 4.

Why are electrostatic (ion-pair) interactions much stronger in a protein's hydrophobic interior than on its surface?

The interior is nonpolar (low dielectric, similar to vacuum), so charges are not 'shielded'; the surface is exposed to water (high dielectric, epsilon=80), which screens/weakens the electrostatic attraction.

Rank hydrogen bonds, van der Waals interactions, and ion pairs by typical strength (strongest to weakest).

Ion pairs (electrostatic) > hydrogen bonds > van der Waals interactions (though ion pairs remain strong at longer range, while van der Waals and H-bonds have a shorter optimal distance).

Per Table 2.1, what is the approximate energy range for a charge-charge (ionic) interaction?

-13 to -17 kJ/mol.

Per Table 2.1, what is the approximate energy range for a charge-dipole interaction (H-bond)?

-13 to -21 kJ/mol.

Per Table 2.1, what is the approximate energy range for a dipole-dipole interaction (H-bond)?

-2 to -8 kJ/mol.

Per Table 2.1, what is the approximate energy range for a van der Waals interaction?

-0.4 to -0.8 kJ/mol.

What causes aromatic pi-stacking interactions?

Dispersion (induced dipole-induced dipole) forces; pi-bonds are more polarizable than sigma bonds, producing a stronger induced dipole between stacked aromatic rings.

In DNA, roughly how many van der Waals contacts occur in a set of two stacked base pairs?

About 15 van der Waals contacts.

Rank P, C, N, H, O, S from lowest to highest electronegativity.

P < H < C < S < N < O (approximately; P and H are close, as are C and S).

Rank these hydrogen bonds from weakest to strongest: S-H…O, N-H…O, O-H…O.

S-H…O (weakest) < N-H…O < O-H…O (strongest) -- strength increases with the electronegativity of the donor atom.

Rank cyclohexyl-SH, cyclohexyl-NH2, cyclohexyl-OH, and cyclohexyl-CO2H by increasing H-bond donating ability toward methylamine.

-SH < -NH2 < -OH < -CO2H (weakest to strongest); donor strength increases with the electronegativity/acidity of the donating group.

Why is water an excellent solvent for NaCl, while hexane is not, even though neither has a formal charge?

Water's permanent dipole forms ion-dipole hydration shells around Na+ and Cl-, and its high dielectric constant (80) screens/weakens the ionic attraction between them. Hexane is nonpolar (no dipole), cannot hydrate the ions, and has a low dielectric constant, so it cannot stabilize separated ions.

Would benzene or cyclohexane show stronger intermolecular van der Waals interactions in pure solution, and why?

Benzene -- its planar, delocalized pi-electron system is more polarizable than cyclohexane's sigma-bonded ring, allowing stronger induced-dipole (dispersion/pi-stacking) interactions between molecules.

What is a clathrate (or 'flickering cluster')?

An ordered, hydrogen-bonded cage of water molecules that forms around a nonpolar (hydrophobic) solute.

What thermodynamic quantity actually drives the hydrophobic effect?

Entropy -- minimizing the ordered water shell around nonpolar surfaces increases the entropy of the surrounding water.

True or False: the hydrophobic effect is caused by an intrinsic attractive force between nonpolar groups.

False -- it is driven by the increase in entropy of water that occurs when ordered water molecules around nonpolar surfaces are minimized/released, not by direct attraction between the nonpolar groups themselves.

When hydrophobic molecules cluster together (e.g., forming a micelle), what happens to the entropy of the system, and why?

Entropy increases, because fewer water molecules are forced into an ordered cage around the (now-reduced) hydrophobic surface area.

When an enzyme binds a substrate, what happens to the ordered water molecules that previously surrounded both surfaces?

They are displaced/released into the bulk solvent as disordered water, which increases entropy and helps stabilize the binding interaction (along with new H-bonds, ionic, and hydrophobic contacts).

Approximately what percent of human cell mass is water?

About 70%.

Approximately what percent of human cell mass is protein?

About 15-20%.

What structural feature makes a molecule 'amphipathic'?

It has both a polar/hydrophilic region and a nonpolar/hydrophobic region.

What is the Gibbs free energy equation?

delta-G = delta-H - T x delta-S.

What does a negative delta-G indicate about a reaction?

It is spontaneous / exergonic.

What does a positive delta-G indicate about a reaction?

It is non-spontaneous / endergonic (the reverse reaction is favorable).

What does delta-G = 0 indicate?

The system is at equilibrium (reversible).

What is the relationship between delta-G-standard-prime and Keq?

delta-G_degree-prime = -RT ln(Keq).

If Keq > 1, what is the sign of delta-G-degree-prime, and which direction is favored?

Negative; formation of products is favored.

If Keq < 1, what is the sign of delta-G-degree-prime, and which direction is favored?

Positive; formation of reactants is favored.

What are the 'biochemical standard conditions' used to define delta-G-degree-prime?

Constant pressure (1 atm), room temperature (298 K), [reactants] = [products] = 1 M initially, pH 7.0, and standard [H2O].

What equation relates the actual delta-G under cellular conditions to delta-G-degree-prime?

delta-G = delta-G-degree-prime + RT ln(Q), where Q is the mass-action ratio.

What is the mass-action ratio Q, and how does it differ from Keq?

Q = [products]/[reactants] at any given (not necessarily equilibrium) moment, using actual concentrations; Keq is specifically the ratio at equilibrium.

How do cells drive a thermodynamically unfavorable reaction (delta-G > 0) forward?

By coupling it to a strongly favorable (exergonic) reaction, such as ATP hydrolysis, so that the summed delta-G of the coupled reactions is negative.

Why might a thermodynamically favorable reaction (delta-G < 0) not actually proceed at a noticeable rate (e.g., diamond to graphite)?

Because thermodynamics only describes favorability/direction, not rate; the reaction may have a large activation energy barrier (delta-G-double-dagger), making it kinetically very slow.

What can lower a reaction's activation energy barrier without changing delta-G?

A catalyst, such as an enzyme.

The isomerization of Glucose-6-P to Fructose-6-P has delta-G-degree-prime = +1.7 kJ/mol, yet proceeds forward in glycolysis. How is this possible?

Because actual cellular concentrations of glucose-6-P and fructose-6-P are not 1 M each; using delta-G = delta-G-degree-prime + RT ln(Q) with the real (low, unequal) concentrations gives a negative delta-G, making the reaction favorable under cellular conditions.

Convert a C-C bond energy of 350 kJ/mol into kcal/mol.

About 83.7 kcal/mol (350 / 4.184 kJ per kcal).

What is the approximate length of a C-C bond?

About 1.5 Angstroms (0.154 nm).

What is the three-letter code, one-letter code, and side chain functional group of Alanine?

Three-letter: Ala; One-letter: A; Functional group: alkane.

What is the three-letter code, one-letter code, and side chain functional group of Cysteine?

Three-letter: Cys; One-letter: C; Functional group: thiol.

What is the three-letter code, one-letter code, and side chain functional group of Aspartate (aspartic acid)?

Three-letter: Asp; One-letter: D; Functional group: carboxylic acid.

What is the three-letter code, one-letter code, and side chain functional group of Glutamate (glutamic acid)?

Three-letter: Glu; One-letter: E; Functional group: carboxylic acid.

What is the three-letter code, one-letter code, and side chain functional group of Phenylalanine?

Three-letter: Phe; One-letter: F; Functional group: phenyl.

What is the three-letter code, one-letter code, and side chain functional group of Glycine?

Three-letter: Gly; One-letter: G; Functional group: hydrogen.

What is the three-letter code, one-letter code, and side chain functional group of Histidine?

Three-letter: His; One-letter: H; Functional group: imidazole.

What is the three-letter code, one-letter code, and side chain functional group of Isoleucine?

Three-letter: Ile; One-letter: I; Functional group: alkane.

What is the three-letter code, one-letter code, and side chain functional group of Lysine?

Three-letter: Lys; One-letter: K; Functional group: amine.

What is the three-letter code, one-letter code, and side chain functional group of Leucine?

Three-letter: Leu; One-letter: L; Functional group: alkane.

What is the three-letter code, one-letter code, and side chain functional group of Methionine?

Three-letter: Met; One-letter: M; Functional group: thioether.

What is the three-letter code, one-letter code, and side chain functional group of Asparagine?

Three-letter: Asn; One-letter: N; Functional group: amide.

What is the three-letter code, one-letter code, and side chain functional group of Proline?

Three-letter: Pro; One-letter: P; Functional group: (cyclic) alkane.

What is the three-letter code, one-letter code, and side chain functional group of Glutamine?

Three-letter: Gln; One-letter: Q; Functional group: amide.

What is the three-letter code, one-letter code, and side chain functional group of Arginine?

Three-letter: Arg; One-letter: R; Functional group: guanidinium.

What is the three-letter code, one-letter code, and side chain functional group of Serine?

Three-letter: Ser; One-letter: S; Functional group: alcohol.

What is the three-letter code, one-letter code, and side chain functional group of Threonine?

Three-letter: Thr; One-letter: T; Functional group: alcohol.

What is the three-letter code, one-letter code, and side chain functional group of Valine?

Three-letter: Val; One-letter: V; Functional group: alkane.

What is the three-letter code, one-letter code, and side chain functional group of Tryptophan?

Three-letter: Trp; One-letter: W; Functional group: indole.

What is the three-letter code, one-letter code, and side chain functional group of Tyrosine?

Three-letter: Tyr; One-letter: Y; Functional group: phenol.

Which amino acid has the three-letter code Ala and one-letter code A?

Alanine (functional group: alkane).

Which amino acid has the three-letter code Cys and one-letter code C?

Cysteine (functional group: thiol).

Which amino acid has the three-letter code Asp and one-letter code D?

Aspartate (aspartic acid) (functional group: carboxylic acid).

Which amino acid has the three-letter code Glu and one-letter code E?

Glutamate (glutamic acid) (functional group: carboxylic acid).

Which amino acid has the three-letter code Phe and one-letter code F?

Phenylalanine (functional group: phenyl).

Which amino acid has the three-letter code Gly and one-letter code G?

Glycine (functional group: hydrogen).

Which amino acid has the three-letter code His and one-letter code H?

Histidine (functional group: imidazole).

Which amino acid has the three-letter code Ile and one-letter code I?

Isoleucine (functional group: alkane).

Which amino acid has the three-letter code Lys and one-letter code K?

Lysine (functional group: amine).

Which amino acid has the three-letter code Leu and one-letter code L?

Leucine (functional group: alkane).

Which amino acid has the three-letter code Met and one-letter code M?

Methionine (functional group: thioether).

Which amino acid has the three-letter code Asn and one-letter code N?

Asparagine (functional group: amide).

Which amino acid has the three-letter code Pro and one-letter code P?

Proline (functional group: (cyclic) alkane).

Which amino acid has the three-letter code Gln and one-letter code Q?

Glutamine (functional group: amide).

Which amino acid has the three-letter code Arg and one-letter code R?

Arginine (functional group: guanidinium).

Which amino acid has the three-letter code Ser and one-letter code S?

Serine (functional group: alcohol).

Which amino acid has the three-letter code Thr and one-letter code T?

Threonine (functional group: alcohol).

Which amino acid has the three-letter code Val and one-letter code V?

Valine (functional group: alkane).

Which amino acid has the three-letter code Trp and one-letter code W?

Tryptophan (functional group: indole).

Which amino acid has the three-letter code Tyr and one-letter code Y?

Tyrosine (functional group: phenol).

Which amino acids have an alkane (simple hydrocarbon) side chain?

Alanine, Isoleucine, Leucine, Valine (and Proline, whose side chain is a cyclic alkane).

Which amino acids have an alcohol side chain?

Serine and Threonine.

Which amino acids have an amide side chain?

Asparagine and Glutamine.

Which amino acids have a carboxylic acid side chain?

Aspartate and Glutamate.

Which amino acid has a thiol side chain?

Cysteine.

Which amino acid has a thioether side chain?

Methionine.

Which amino acid has a phenyl (benzene ring, no substituent) side chain?

Phenylalanine.

Which amino acid has a phenol side chain?

Tyrosine.

Which amino acid has an indole side chain?

Tryptophan.

Which amino acid has an imidazole side chain?

Histidine.