The Effect of Entropy on Protein Folding

L.Strube

Abstract
This article concerns the modern challenge of determining a pro-
tein’s tertiary structure and folding mechanism based on its primary
amino acid sequence. We explore the concept of entropy as an influ-
ential factor in this process by describing a mathematical model for
the ”attractive force” of two large macromolecules, modeled as hard
spheres, immersed in a low-concentration solution of particles, repre-
sented as small hard spheres. Using this model we demonstrate that
the greatest entropy of the small particles occurs when the surfaces of
the two large macromolecules are in contact. In addition,we describe
a recent extension of this model to solutions of high small-particle
concentration. Finally we discuss a current application of this model
to protein research.

1 Introduction
In 2003 the Human Genome project was completed, having determined the
nucleotide sequence of the last gene in the last molecule of human DNA [14].
As each gene within a molecule of DNA codes for the amino acid sequence of
a specific protein, this event marked the beginning of a new era in molecular
biology,an era in which the quantity of known protein sequences far exceeds
the quantity of known protein structures [5].

1.1 Protein Structure Determination

The gap between the volume of known protein sequences and the volume of
known protein structures is due both to the complexity of protein molecules
and the technologies currently available to scientists [5]. A protein’s complex
structural organization consists of four distinct levels: primary, secondary,

1
tertiary and quaternary (Figure 1). The primary level consists of the amino
acid sequence coded for by individual genes and can be visualized as a linear
arrangement of amino acid ”beads”. The twisting and folding of this ”string
of beads” into α-helices and β-pleated sheets forms the protein’s secondary
structure which then folds in on itself to form the protein’s tertiary struc-
ture. Each of these first three levels of organization consists of the twists
and folds of a single amino acid sequence known as a peptide. While many
proteins contain only one peptide, some are formed via the aggregation of
multiple strands. Such proteins are described as having a quaternary struc-
ture which forms when multiple peptides, of tertiary structure, bind into a
single, functioning aggregate [16].

Figure 1: The Four Levels of Protein Structure [19]

Without a knowledge of the gene sequence that codes for a specific pro-
tein, both the determination of its structure and the determination of its
sequence requires involved chemical protocols. [5]. However, if the gene

2
sequence ”code” for a protein is known, then the gene sequence can be
translated into the corresponding protein sequence in a fairly straightfor-
ward manner. Thus, while protein structure determination continues to be
a tedious process, the rate of protein sequence determination has increased
rapidly since the completion of the Human Genome Project [5].
As a protein’s function is tied tightly to its overall structure, this flood
of new sequences represents a gold-mine of scientific breakthroughs, if the
corresponding structures can be determined [21]. Thus, the volume of known
protein sequences is serving as a catalyst for the development of new predic-
tive structure determination methods. These methods aim to use a protein’s
amino acid sequence as a ”bottom-up” predictor of its final structure. This
is in contrast to the ”top-down” classical methods such as x-ray crystallogra-
phy and NMR spectroscopy which determine protein structure via protocols
which analyze the chemical characteristics of the structures as a whole [5].

1.1.1 Modern Sequence-Based Methods

Sequence Comparison
Current prediction methods are divided into two general categories based on
the strategy used [5]. The first category utilizes the fact that a protein’s struc-
ture is primarily determined by the identity of the amino acids it contains. In
other words, proteins with similar sequences typically produce similar over-
all structures and thus have similar functions [15] [5]. Scientists using this
method compare new protein sequences, those with unknown structure, to
the sequences of proteins whose structures have already been determined by
classical methods. This method has proved to be relatively accurate, exhibit-
ing a success rate similar to that of low resolution crystallography and NMR
[20].

The ab initio Method

The second strategy of prediction attempts to determine a protein’s structure
based on the energetics involved without any comparison to known structures
[5][20]. It involves the development of both an energy function and a search
protocol by which all possible configurations of a given sequence can be eval-
uated. This method is based on the thermodynamic hypothesis which states
that the protein structure with the lowest free energy is the native (natural)
state structure [5] [18]. This category of structure prediction is often referred

3
to as the ab initio (lit. ”in the beginning”) or de novo (”lit. anew”) method
in reference to its focus ”bottom up” structure prediction [20] [6] [1] [11].
Currently the ab initio method is, in theory, the most valuable of the two
structure prediction categories in that it is not limited by the diversity (or
lack thereof) of classically determined protein structures. Further, by pre-
dicting a protein’s structure from its sequence alone, scientists could detect
structural, and thus functional, similarities between proteins with very dif-
ferent sequences. However, at this time the success rate of ab initio structure
prediction is quite low, a fact which appears to be the result of our limited
understanding of electrostatics and solvent/protein interactions [20]. Thus
the improvement of this valuable method of requires further research into
each of these factors.
It is in the search to understand these factors that two fields of study
meet: the field of protein structure determination we have been discussing,
and the field of protein folding research. While to the casual observer these
two fields appear to be one and the same, they are in fact at their core quite
distinct in their focus. The former ”determination” field is primarily focused
on the end result of protein folding while the later ”folding” field is primarily
interested in the process by which a protein folds. Thus while the same forces
and environmental influences affect both a protein’s final structure and the
manner by which it folds, these two topics represent branches of two distinct
fields: molecular biology and the study of self-assembly.

1.2 The study of Self-Assembly

1.2.1 Nanotechnology
The study of self-assembly is a fairly new research area spanning the last two
to three decades. However, it is perhaps more accurately understood as a
natural outgrowth of the development of nanotechnology which was inspired
by living systems and first introduced in the 1950’s [18]. In an era of room-
sized computers, when the structure of DNA had just been elucidated, the
concept of nanotechnology held an almost science fiction quality. Richard
Fenymann, one of the foremost visionaries in the field of nanotechnology
marveled in his speach ”There’s Plenty of Room at the Bottom” at the
capabilities of the living cell. He exhorted scientists to search for ways to
mimic the cell, saying: ”Many of the cells are very tiny, but they are very
active; they manufacture various substances; they walk around; they wiggle;

4
and they do all kinds of marvelous things-all on a very small scale. Also,
they store information. Consider the possibility that we too can make a
thing very small, which does what we want-that we can manufacture an
object that maneuvers at that level!” [12] [18].
As Dr. Feynmann envisioned, technology has in fact become smaller and
smaller; calculations once performed by room-sized computers can now be
completed on hand-held calculators. However, while smaller size does imply
greater efficiency and lower cost of materials, in reality the tools required to
construct such technology have become quite expensive and is now a limiting
factor in the progress of this field [21]. Thus the need for cost-effective ways
of producing nanotechnology serves as one of the driving forces of the study
of self-assembly. It is hoped that by studying the process by which natural
systems, such as proteins, self-assemble we can artificially create our own
self-assembling nanoscale machines [21].

1.2.2 The Turing Machine

If nanotechnology is the driving force behind the study of self assembly,
then it is the concept of a Turing machine that is the foundation for the
field. The concept of a Turing machine was developed in the early 1900’s
by Alan Turing [18]. His idea was that any function or operation could be
broken down into a sequence of discrete actions and that by following such
a sequence of actions the end result would always be the same [7]. His ideas
marked the birth of algorithmic thinking [18]. Thus, a greater understanding
of solvent interactions is necessary for both protein stucture determination
and for the development of the ”discrete steps” in the Turing Machine of
protein folding.

1.3 Entropy
It has been known for many years that the chemical characteristics of the
amino acids which make up a protein play a significant role in its overall
structure[18]. This influence is due both to interactions between individual
amino acids and to interactions between a given amino acid and its environ-
ment. For example, each amino acid can be classified as charged (positively,
or negatively), polar, or non-polar. If a protein sequence is composed entirely
of negatively charged residues it will not form a helix, the residues repelling
one another like matching ends of a magnet. However, appropriate spacing

5
negatively and positively charged amino acids can lead to the formation of
a helix [16]. Similarly water, being itself a polar molecule, is attracted to
other polar/charged molecules and repelled by non-polar molecules. Thus
non-polar amino acids are likely to orient themselves inside the overall struc-
ture of a protein away from water whereas charged or polar amino acids are
found on the exterior surface of the protein in contact with water [16].
Only in recent years have non-specific interactions between a protein and
its environment been considered. One such interaction now being researched
is the role of entropy in determining a protein’s native (naturally occuring)
structure [22] [13] [17]. Entropy is a measure of disorder, or randomness, in
a system [9]. For example, imagine a flat tray containing a set of checkers
(Figure 2). If you confine these checkers to one corner of the tray their
organization is high, implying a low level of entropy. On the other hand, if
you shake the tray allowing the checkers to disperse where they will, their
organization becomes low, implying a high degree of entropy. The second law
of thermodynamics states that the the universe is tending towards disorder
[9]. Thus reactions which increase entropy are spontaneous and an energy
input is required to prevent an increase in entropy.

Figure 2: Entropy

Using this analogy a cell is essentially a tray of checkers. However, unlike

6
the example above, a cell contains many different objects of different sizes.
Some are relatively large like the proteins we have been discussing, others
such as sodium and potassium ions or free amino acids are quite small. In
addition the cell is an aqueous environment and its contents being immersed
in solution of high water concentration [10]. Recently it has been proposed
that an increase in the entropy of the small particles within a cell may be a
driving force favoring the organized folding of protein structures [22] [13] as
well as the aggregation of protein/DNA complexes [17].

2 Interaction between Particles Suspended in

Solutions of Macromolecules
As cells are essentially fluid filled compartments, any revelent model of inter-
actions between particles within a cell must involve solution/solute scenario.
The fundamental model for non-specific interactions between particles in
solution was produced by Asakura and Oosawa in the 1950’s [3][4] and is
the basis for multiple modern models involving protiens [17][13][22]. In the
Asakura and Oosawa (AO) model, the authors focused primarily on the effect
of entropy on macromolecule aggregation. In doing so they chose to ingnore
interactions between solutes due to charge or polarity.

2.1 Osmotic Pressure as an Attractive Force

To understand the AO model, imagine two metal plates immersed in a solu-
tion containing only small particles (diameter = d) (Figure 3). Observe that
if the plates are oriented such that the distance between the plates is less
than d, the small particles are excluded from the space between the plates.
This produces a concentration gradient from the region of pure solvent be-
tween the plates, to the region of higher particle concentration surrounding
the plates. As a result, an osmotic force acts on the system causing pure
solvent to rush out of the interior space, diluting the exterior solution, and
pulling the plates together [23]. Referring back the the ”tray of checkers”
analogy above (Figure 2), this scenario causes the metal plates to become
more organized, having been pulled together, while the small particles be-
come less organized, having been given a greater free volume in which to
disperse.

7
Figure 3: Two metal plates suspended in a solution with particles of diameter
d

This idea can then be generalized to a system containing two large macro-
molecules (diameter = D) suspended in a similar solution of small particles
(diameter = d), such that the distance between the large macromolecules
is less than d. As in the case of the metal plates, the small particles are
excluded from the region between the macromolecules and a force equivalent
to osmotic pressure acts on the outer edges of the macromolecules driving
them together and increasing the entropy of the small particles (Figure 4).

8
Figure 4: Two hard spheres of diameter D suspended in a solution of particles
with diameter d

The goal of the AO model was to quantify this ”attractive” force acting
on the surface of a macromolecule. Once quantified, this attractive force
can then be integrated to determine the change in free energy resulting from
a change in the macromolecules’ orientation relative to one another. As
energy is required to prevent an increase in entropy, energy and entropy are
essentially two sides of the same coin: an increase in free energy corresponds
to a decrease in entropy and an increase in entropy corresponds to a decrease
in free energy. Thus determining the change in free energy is mathematically
equivalent to determining the change in entropy. If we let a represent the
distance between the centers of the two large macromolecules, minimizing
the free-energy function for this system in terms of a yields the separation
distance at which the system exhibits the greatest small-particle entropy.

2.2 Quantifying the Attractive Force

The first step in determining the value for a which produces the greatest
entropy, is to quantify the force acting on single large macromolecule. This

9
pressure can be expressed as:
Z Z Z
P = ρ(x)∇w(x, a)d−
→
x (1)
V

where − →
x is a position vector from the center of the large macromolecule to
the center of the small particle concentration(Figure 5), ρ(x) is the numerical
density of the small particles at the position x, a is the distance between the
two large macromolecules and ∇w(x, a) represents the gradient of the average
potential energy of a small particle at x which results from the forces acting
on it.[3] [23].

Figure 5: Position Vector

2.2.1 Statistical Mechanics: Approximating ρ(x)

Several challenges arise when using this equation. The first is determining
ρ(x), the density of the small particles. To find ρ(x), Asakura and Oosawa
assumed that the concentration of the small particles in solution was low,

10
and used a first-order approximation of a statistical mechanics equation to
determine their density [8]. This first order approximation is equivalent to
Boltzman’s equation and is expressed as:
w(x,a)
ρ(x) = N e− KT (2)
Substituting this into equation (1) for P yields:
Z Z Z
N e− KT ∇1 w(x, a)d−
→
w(x,a)
P = x
V
where N represents the concentration of particles, K is the Boltzman con-
stant, and T is absolute temperature. As before, w(x, a) represents the av-
erage potential energy of a small particle at x which results from the forces
acting on it when the centers of the two large macromolecules are separated
by a distance a.
In the specific scenario we are considering this equation further simplifies
to the following:
∂
P = kT N (ln Q) (3)
∂a
Z
−w(x,a)
Q= e kT dx. (4)
V

2.2.2 Q as the Free Volume

The second challenge in using this equation is determining the energy, w,
of the small particles; however, in this scenario Q is equivalent to the free
volume available to the centers of the small particles [3] [4]. To determine the
value for Q, note that surrounding each of the large macromolecule spheres
there exists a shell of depth d2 into which the centers of the small particles
cannot enter (Figure 6). Also note that if the spheres are at a distance greater
than d apart, that is, if the small particles can invade the space between the
macromolecules, the space excluded from the center of the small particles has
a volume equal to that of the two spheres and their shells. If on the other
hand, the shells overlap, the volume of the excluded space is reduced by the
volume of the overlapping region.

11
 Figure 6: The Overlap Region

To determine the Q, the free volume available to the small particles, we

begin by calculating volume of the overlapping region of the shells(Figure 7).
First let a equal the distance between the centers of the spherical macro-
molecules and fix the centers of the two macromolecules at (0, 0, a2 ) and
(0, 0, − a2 ). Observe that if the overlapped region is divided in two longi-
tudinally that each half of this region is a portion of a sphere of radius D+d
2
(Figure 4) and has a depth of a2 (Figure 7). Thus to find the volume of the
overlapping region we find the volume of one sphere portion and multiply
by two. To simplify the computation let R = D+d 2
, h = a2 . Note that the
upper bound of the volume to be calculated is z = 0 and the lower bound is
described by the following equation:

x2 + y 2 + (z − h)2 = R2

12
 Figure 7: Half the Volume of the Overlap Region

Using polar coordinates (r2 = x2 + y 2 ), the following integral can be used

to determine the volume of this ”half” region:
Z 2π Z √R2 −h2 h√ i
Vhalf = R2 − r2 − h rdrdθ
0 0
with the entire volume of the overlapping region equaling:
Z 2π Z √R2 −h2 h√ i
Voverlap = 2 R2 − r2 − h rdrdθ.
0 0
Next we integrate:
Z √R2 −h2 h√ ÃZ √ Z √ !
i R2 −h2 √ R2 −h2
4π R2 − r2 − h rdr = 4π R2 − r2 rdr − hrdr .
0 0 0

Integrating again gives:

· ¸ · ¸
(h2 )3/2 (R2 )3/2 R2 h h2 h 4 3 3 3 2 3 3
Voverlap = 4π − + − + = π −h + R − R h + h .
3 3 2 2 3 2 2

13
Therefore the total volume of the excluded space can be calculated as follows:
µ ¶ · ¸
4 3 4 3 3 2 1 3
Vexcluded = 2 πR − π R − R h + h
3 3 2 2
· ¸
4 3 4 3 4 3 3 2 1 3
= πR + πR − π R − R h + h
3 3 3 2 2
· ¸
4 4 3 1
= πR3 − π − R2 h + h3
3 3 2 2
· ¸
4 3 1
= π R 3 + R 2 h − h3 .
3 2 2
D+d
Substituting R = 2
and h = a2 back into our solution yields:
"µ ¶3 µ ¶2 #
4 D+d 3 D + d ³ a ´ 1 ³ a ´3
Vexcluded = π + − .
3 2 2 2 2 2 2

Thus the free volume Q can be described by:

"µ ¶3 µ ¶2 #
4 D+d 3 D + d ³ a ´ 1 ³ a ´3
Q = Vtotal − Vexcluded = Vtotal − π + −
3 2 2 2 2 2 2
· ¸
π 2 1
= Vtotal − (D + d)2 + (D + d)2 a − a3 .
4 3 3

Note: Based on these calculations and our specific definition of Q, when there
is no overlap, i.e. a ≥ D + d, we have:
µ ¶3
8 D+d
Q = Vtotal − π .
3 2

We can now use this form of Q to get an expression for P , namely,

P = −po S
kT N
where po = V
.

14
2.2.3 Assumption: V À the Excluded Space
Recalling our original formula (Equation 3) for P we have:

∂
P = kT N (ln Q)
∂a
kT N
=− S
V
= −po S

Thus our equation for S can be written as follows:

∂
S = −V (ln Q)
∂a
Q0
= −V
Q
"¡ ¢ #
π 2 2
4
[(D + d) − a ]
=
1 − ExcludedSpace
V

If we assume that the small particle concentration is low and the volume
V of our region is significantly larger than the excluded volume we can make
the following approximation:
³π ´ £ ¤
S≈ (D + d)2 − a2 (5)
4
This in turn produces the following tractable approximation for P when
a ≤ (D + d): ³π ´ £ ¤
P ≈ −ρ (D + d)2 − a2
4
Note that based on this approximation and our definition of Q above, if
a ≥ (D + d) then P = 0.

2.3 Determining the Free Energy Equation

Recall that F orce = 4Energy [2]. To determine the potential energy of our
scenario we compute the following:

15
 Z
U (a) = − P da
Z
π £ ¤
=ρ (D + d)2 − a2
4
· ¸
π 2 a3
= −ρ −(D + d) a + +c
4 3
To determine c we set U (D + d) = 0 and solve:
· ¸
3 (D + d)3
U (D + d) = −(D + d) + +c =0
3
· ¸
2(D + d)2
= − +c =0
3

2
Thus we have c = 2 (D+d)
3
which results in the following free-energy equation:

( h i
a3 2(D+d)2
−ρ π4 −(D + d)2 a + + : a ≤ (D + d)
U (a) = 3 3
0 : a ≥ (D + d)
If we assume that D À d, this equation simplifies to:
( h i2
3 (D+d−a)
− 2 kT θβ : a ≤ (D + d)
U (a) = d (6)
0 : a ≥ (D + d)
D
where θ is the volume concentration of the macromolecules and β = d
.

2.4 Minimizing Free-Energy ∼ Maximizing Entropy

From this approximation it is clear that the free-energy U (a) is minimized
when a=(D+d). In other words, the free-energy of the system reaches a
minimum when the surfaces of the macromolecules are in contact. As a
free-energy minimum represents an entropy maximum we may state that
entropy reaches a maximum when the macromolecules are in contact. While
this result was achieved by assuming a low concentration of small particles
Asakura and Oosawa hypothesized that it would also be applicable at high
concentrations as well [4].

16
3 Relaxing an Assumption: A High Concen-
tration Scenario
It is important to note that the development of the free energy approxi-
mation U (a) required multiple assumptions which must be evaluated before
these results can be applied to the problem of protein folding and structure
determination. The first of these assumptions was that the concentration of
small particles was low (Equation 2), the second, that the total volume to
excluded space ratio is high (Equation 5), and the third that the diameter
D of the large macromolecules is significantly larger than the diameter d of
the small particles (Equation 6). In addition the macromolecules were mod-
eled as spheres whereas proteins themselves are far more complex as noted
previously.
The third of these assumptions, D À d is fairly reasonable as proteins
are significantly larger than the free amino acids, ions, and water molecules
surrounding them; however, the first and second assumptions both depend on
a low concentration of small particles. If we let these small particles represent
water molecules these two assumptions are clearly violated, the cell being an
aqueous environment.
In 1994, Walz and Sharma revisited the AO model recalculating the at-
tractive force for higher concentrations of small particles [23]. They did this
by returning to the statistical mechanics equation used to approximate ρ(x),
using a second-order approximation of the density of the small particles in-
stead of the first-order approximation described in the AO model. In doing
so they found that while an increase in entropy certainly acts as an attractive
force at separations D ≤ a ≥ (D + d), it also serves as a repulsive force at
separations (D + d) ≤ a ≥ 2(D + d) (Figure 8).

17
 Figure 8: Increase in Entropy as a Repulsive Force

On the surface the presence of a repulsive barrier to the aggregation of

the large macromolecules appears to limit the applicability of the AO model
with regards to living systems. However, osmotic pressure as it relates to
this scenario, is not the only force acting on proteins within cells, nor is it
the strongest. In fact Walz and Sharma noted in their article Effect of Long
Range Interactions on Depletion Force between Colloidal Particles that the
weakness of this force has proved to be an obstacle in the direct experimental
study of the scenario described by the AO model [23]. Thus in the crowded,
energy-rich environment of the cell, the likelihood that two portions of a
protein molecule will enter the ”attractive” range is high [17] and the AO
model can be used as a basic model for proteins in solution.

18
4 Discussion: The AO Model Applied to Pro-
tein Folding
In recent years the AO model has been applied to the problem of protein
folding in hopes that doing so will improve the accuracy of folding models
[13]. In 2005, Harano and Kinoshita noted that the problem of protein folding
is one of the most difficult problems facing molecular biology today. They
also noted that the isolated folding of a protein results in a decrease of the
protein’s entropy. Thus for such a reaction to occur spontaneously it must
be coupled to an energetically favorable reaction [13]. Prior to their work,
hydrogen bonding, hydrophobic effects and the formation of salt bridges had
been studied as potential ”favorable” reactions. In each case the results were
inconclusive, thus Harano and Kinoshita chose to explore possibility that an
increase in the entropy of water could serve as the energetically favorable
reaction coupled to protein folding [13].
They found that due to the small size and hence high numerical concen-
tration of water in aqueous living systems, the entropic gain of water was
sufficient to counterbalance even the largest entropy losses due to protein
folding. They also noted that if cells contained a solvent with a larger molec-
ular size, such a counterbalance would not occur as the increase in solvent
entropy would not be sufficient to counter balance protein folding [13].

5 Conclusion
We see that the problem of protein folding and structure determination is a
significant open problem today, so significant that it has been described by
some as the ”holy grail” of molecular biology [15]. Due to the vital role of pro-
teins within living organisms and their ability to self assemble, the solution
to this problem has far reaching ramifications for both molecular biology and
nanotechnology. Currently, self-assembling drug carriers are being used to
deliver drugs to the cancerous tissue of patients and an increased understand-
ing of self-assembly is expected to result in further medical breakthroughs as
well as to aid the development of microcomputers and other nanotechnologies
[21].
Scientists, mathematicians and physicists are approaching this problem
from a variety of perspectives including classical methods such as x-ray crys-
tallography and NMR, comparative methods by which new protein structures

19
are approximated via comparison to know structures, and ab initio structure
prediction which attempts to predict protein structure using energy func-
tions and search protocols. Despite the extensive work being done, a correct
elucidation of the protein folding process has yet to be determined and pre-
diction models continue to exhibit limited accuracy [13] [20]. As a result,
study is now focusing on individual forces and environmental characteristics
that influence protein folding [20] [13].
One such influence, currently being researched is the favorable increase in
water entropy which occurs when the amino acids of protein molecules come
into close proximity with one another. The mathematical model developed
by Asakura and Oosawa in the 1950’s for non-interacting hard particles in
solution forms the foundation of this work. A recent extension of this model
by Harano and Kinoshita suggests that the favorable increase in entropy of
water molecules within a cell is sufficient to overcome the entropic loss of the
protein molecule itself as it folds. Harano and Kinoshita further note that
such a counterbalance of entropic gain and loss is dependent on the small
size of water molecules and suggest that favorable protein folding would not
occur in other solvents [13].
From this work it is apparent that a further understanding of the pro-
tein folding and structure determination is dependent on the integration of
multiple fields of study including chemistry, physics, biology and mathe-
matics. Such an integration requires scientists and mathematicians to be
well-rounded in their knowledge of these subjects as well as to engage in
collaborative work with individuals outside their immediate field. It is only
through this collaboration that further breakthroughs in our understanding
of these complex biological structures is possible.

Acknowledgements I would like to thank Dr. Beckham for his enthusi-

astic and untiring support in what turned out to be a very challenging topic,
Dr. Kreft for her willingness to explain ”basic” physics assumptions to a
couple of literal mathematicians, and my roommate Carrie for all the late
night entropy conversations.

20
6 Epilogue
When I began senior seminar in August I had conflicting expectations. On
the one hand I had completed two other seminar-like math experiences in the
past and so I felt equipped for the challenge. On the other hand I suspected
that choosing ”my own” topic would prove more than I had bargained for.
As it turned out, there was an element of truth in each of these. The skills
I learned in my previous projects were helpful in this class, but I had much
more to learn and while this class was more than I bargained for, I learned
that research is not a solo endeavor and ”more than I bargained for” is just
about right if I’m willing to ask for help.
Of all of the aspects of this seminar, two of my most significant learning
experiences were the process of researching an interdisciplinary topic and
the opportunity to discuss the concepts I studied with a mathematician,
chemist, two physicists and a biochemist. In terms of research I learned that
it is important to read multiple papers addressing the same general topic
rather than sequentially beating my way through one difficult paper. I also
discovered that sometimes a ”follow-up” paper describes the ideas at hands in
a more through and approachable manner than the original. Finally, learned
that one way to analyze the validity and relevance of a paper is to determine
how many times it has been cited in other articles.
In terms of discussing ”my research” with others, I learned that discussion
is one of my favorite parts of the process of learning a new topic. I have
always loved meeting with professors to talk with them about class material,
but it was a completely different experience to discuss material that was
new to both myself and the professor. In addition it was fascinating, albeit
frustrating at times, to see how multiple fields approach the same problem
from very different perspectives. It was also encouraging to watch other
people get excited and interested in what I was studying.
Overall I would describe this experience as one of the most important
of my college career. As much as it freaked me out at times not to see
where I was headed, looking back I realize that this was probably one of the
most important parts of the experience. Without the ability to learn new
”unplanned” ideas I would never be able to mature past the comparatively
”passive” stage of student into an active researcher. Given my experience I
wish that undergraduates were required to participate in multiple seminars
over the course of their college career.

21
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