Download 6b. Thermodynamics

Structural Biology
Thermodynamics
The First Law of Thermodynamics is
the Law of Conservation of Energy
Anything that happens spontaneously, that is, without an input of energy,
will result in molecules being more disorganized, more random, more
mixed together, and more spread out.
• Keep in mind that energy released in an
exergonic reaction is not necessarily
released as heat.
an exergonic (energy releasing) reaction is not
necessarily exothermic (heat releasing).
• a reaction with a negative Δ G (free energy)
value may have either a positive or
negative ΔH (enthalpy) value!
• ENTALPY is a measure of the internal energy of
a system.
• the change in internal energy between reactants
and products can be measured by the heat
absorbed or released during the course of a
reaction
Kinetics vs Thermodynamics!
• It is important to mention that a chemical reaction has kinetic and
thermodynamic aspects.
▫ The quantity related to kinetics is the rate constant k; this constant is
associated with the activation energy required for the reaction to move
forward, that is, the reactivity of the reactants.
▫ The thermodynamic quantity is the energy difference resulting
from the free energy (ΔG) given off during a chemical reaction, that is,
the stability of the products relative to the reactants.
• Matter seeks to be in its lowest energy state. This
is a universal law.
• when a substance is at lower energy, it is at a
more stable state.
• The relative energies of reactants and products
decide the Thermodynamic stability
Thermodynamic stability can be
defined in different ways.
• Reactants that convert in to products with the release of energy
(Exothermic reactions) can be termed as thermodynamically
stable.
• Some reactions do not take place on their own.
• They require activation energy to initiate the reaction.
• The reaction that occurs with minimum amount of activation
energy and which will give products with the release of energy,
that is more than what is required to initiate the reaction,
results in thermodynamically stable products.
• If the ∆G is negative, meaning the
products are at a lower energy than the
reactants, then the reaction is
thermodynamically favorable,
meaning it has a reasonable likelihood
of proceeding. The ∆G does not indicate
how fast this reaction will happen.
The reactants actually have to reach a higher energy state before they can reach the
low energy state of the products.
The reactants have to scale an "energy wall," called the Energy of Activation (∆ G‡).
Reactions with a high ∆G‡proceed more slowly. On the other hand, reactions with a
lower ∆G‡ proceed faster. Reactions with a lower ∆G‡ have a faster reaction
rate, and are said to be kinetically favorable.
A QUESTION
• Blood collected 20 years ago from a crime scene is being used
for DNA testing at a murder trial to prove the suspect was
indeed at the scene of the crime. The defense lawyer argues
that this test cannot be reliable, since she knows that the
hydrolysis reaction (breakdown) of DNA has a negative Δ G.
She concludes that therefore the DNA degraded
spontaneously after all this time, and is now useless. As an
expert witness for the prosecution, how can you use your
knowledge of biochemistry to explain why she is mistaken?
More details for those who are
interested in!
http://chemwiki.ucdavis.edu/Physical_Chemistry/Eq
uilibria/Chemical_Equilibria/Principles_of_Chemi
cal_Equilibria/Kinetically_vs_Thermodynamically_
Stable
http://chemistry.tutorvista.com/inorganicchemistry/thermodynamic-equilibrium.html
https://www.khanacademy.org/testprep/mcat/biomolecules/principles-ofbioenergetics/v/thermodynamics-vs-kinetics
Measure of heat
Measure of disorder
the sum of bond
energies OF
FORMED
BONDS
SPONTANOUS EVENT…
-∆G
you might imagine that protein folding is an
exothermic process in which folding is driven by a
favorable, negative change in enthalpy.
favorable hydrogen
bonds, electrostatic
interactions, and van der
Waals interactions,
the entropy of the polypeptide
chain decreases dramatically
NOT REALLY
protein folding is DRIVEN BY
ENTHALPY.
However….
• the hydrophobic effect plays a major role in
protein folding in water…..
increase
Thermodynamics of protein folding
negative ΔG implies that the folding process is spontaneous
Polar groups in an aqueous solvent.
ΔHchain favors
the unfolded structure
Because
the backbone and polar groups interact form stronger
interactions with water than with themselves.
ΔHsolvent favors
the folded protein
Because
water interacts more strongly with itself than with the
polar groups in the protein.
polar groups
sum of the ΔHpolar contributions is close to zero, but usually
favors
the folded structure for the protein slightly.
The chain ΔH contributions are positive
the solvent ΔH contributions are negative.
Slightly negative
polar groups
• ΔSchain favors
the unfolded state,
Because the chain is much more disordered in the unfolded state.
• ΔSsolvent favors
the folded state,
Because the solvent is more disordered with the protein in the folded state.
• sum of the ΔSpolar favors
the unfolded state slightly. In other words,
the ordering of the chain during the folding process outweighs the other entropic factors.
• The ΔGpolar that is obtained from the values of ΔHpolar and ΔSpolar for the
polar groups varies somewhat, but usually tends to favor the unfolded protein!!!!!
• the folding of proteins comprised of polar residues is usually a nonspontaneous
process.
• No proteins are made up solely of polar residues;
why do you think this is?
Non-polar groups in aqueous solvent.
• ΔHchain usually favors
the unfolded state slightly.
• Once again, the reason is that the backbone can interact with water in
the unfolded state.
• However, the effect is smaller for non-polar groups, due to the greater
number of favorable van der Waals interactions in the folded state.
• ΔHsolvent for non-polar groups
favors the folded state
Because water interacts much more strongly with itself than it does
with non-polar groups.
non-polar
• sum of the ΔHnon-polar favors folding somewhat.
• The magnitude of the ΔHnonpolar is not very large,
but is larger than the magnitude of the ΔHpolar, which
also tends to slightly favor folding…
non-polar groups
ΔSchain of the favors
the less ordered unfolded state.
However,
the ΔSsolvent highly favors the
folded state,
due to the hydrophobic effect!!!!
During the burying of the non-polar side chains, the solvent
becomes more disordered.
The ΔSsolvent is a major driving force for protein folding.
• The ΔGnon-polar is therefore negative, due largely to the
powerful contribution of the ΔSsolvent.
Conclusion…
Adding together the terms for
ΔGpolar and ΔGnon-polar gives a
Measurements of this value have
shown that the overall
ΔG for protein folding is very
small: only about –10 to –50
kJoules/mol.
slightly negative overall ΔG for protein folding,
and therefore, proteins generally fold spontaneously.
• http://cbc.arizona.edu/classes/bioc462/462a/N
OTES/Protein_Structure/protein_structure.htm