1.

0 Double Slit Experiment

The elegant difference is blurred by quantum mechanics. When a stream of

electrons passed through one slit, a single band is formed, but when electrons
emitted through two slits an interference pattern is formed, but how could a
piece of matters create an interference pattern like waves? Physicists thought
that particles bounced each other and created the interference pattern. This time
they decided to shoot the electrons one at a time, by this method it is impossible
for electrons to interfere with each other. After a time the same interference
pattern is formed. The conclusion was that the single electron leaves as a particle
and becomes a wave of potential then it goes through both slits and interferes
with itself to hit the wall like a particle (The particle is in two places at once), but
mathematically it is even stranger that the electron goes through both slits, it
goes through neither, it goes through just one slit or it goes through just the
other. All of these possibilities are in superposition with each other
(Khutoryansky, 2013).

(Perimeter Institute, 2012)

Figure 1.0 Double-slit apparatus showing the pattern of electron hits on the observing screen
building up over time.
This made the physicist completely puzzled and they decided to install a
measuring device by one slit to see which slit the electrons actually pass through,
but the quantum world is far more mysterious than they could have imagined.
The electron decided to act differently because it felt that the observer watched
it. When they observed the electron, the electron went back to behave like a little
marble, it produced a pattern of two bands and not many interference pattern as
it was expected. Physicists were Perplexed, they asked what is the matter? Is it
Particles or waves? (Khutoryansky, 2013)
After a while they have discovered that, when the electron was observed the
wave function was collapsed.

1.1 The Explanation of double slit experiment

A Physicist called Max Born, one of the founders of quantum mechanics came up
with a new idea for what the wave equation described. Born said that the wave is
not a smeared out of electron or anything else previously encountered in science.
Instead, he declared that electrons are something about a probability wave
(Probability distribution), that is Born argued that the size of the wave that any
location predicts the likelihood of the electron being found there. Where the
wave is big that is not where most of the electrons are, that is where the
electrons are most likely to be, and that is very strange, so the electron on its
own sees a jumble of possibilities (Khutoryansky, 2013). “You are not allowed to
ask where is the electron right now, but you are allowed to ask if I look for the
electron in this little particular of space, what is the likelihood I will find it there,
and that bugs anyone!”(Peter Fisher, 2012).
Finally, it is shown that the implication of this experiment is that matter can have
both wave and particles properties. This is known as “Wave-Particle Duality” or
“Dual Nature of Particles” This is proposed by Louis de Broglie in 1923 leading to
the birth of modern day quantum mechanics. Exhibiting particles or waves
characteristics depends if a detector is observing the matter or not. The second
implication of the double slit experiment is that the outcomes of macroscopic
events can be affected by observation. This is because macroscopic objects are
composed of microscopic particles acting as either waves or particles (Lejuwaan,
2010).
These facts lead to the emergence of De Broglie equation as shown in (1.1) and
(1.2)

λ=h / p (1.1)
f =Ε /h (1.2)

Where λ is the wavelength, h is Planck's constant, f is the frequency, and E is the

total energy of the particle (Phillips, 2003).

The equations (1.1) and (1.2) are equivalently equal to

p=ℏ ω (1.3)
E=ℏk (1.4)

Where ℏ is the modified Planck’s constant (ℏ=h/2 π ), k is the angular wave

number (k =2 π / λ ¿and ω is the angular frequency (ω=2 πf ¿ (Phillips, 2003).
The comparison between planets in a solar system and electrons in an atom was
no longer reasonable. De Broglie’s hypothesis led to the development of quantum
mechanics and subsequently the Schrö dinger equation.
It is important to know the equations (1.1) and (1.2) to understand the concept
of the Schrö dinger equation that will be discussed in the next section.

2. The Schrödinger wave equation

Quantum mechanics is all about solving the Schrö dinger equation. There are
many Schrö dinger equations, each physical scenario for which you want to apply.
Quantum mechanics has its own Schrö dinger equation, they are all slightly
different and all require slightly different solution techniques. The reason why
there are many different Schrö dinger equations is that the situation over under
which you want to solve the Schrö dinger equation enters the Schrö dinger
equation as a potential function and we know that potential function influence
the physics of quantum mechanics.
The Schrö dinger equation is a wave equation that describes the behavior of
particles by taking account the fact that matter also has these wave-like
properties. “The role of the Schrö dinger equation in quantum mechanics is
analogous to that of Newton’s Laws in classical mechanics. Both describe motion.
Newton’s Second Law is a differential equation which describes how a classical
particle moves, whereas the Schrö dinger equation is a partial differential
equation which describes how the wave function representing a quantum
particle ebbs and flows. In addition, both were postulated and then tested by
experiment” (Phillips, 2003). The Schrö dinger wave equation helped in the
emergence of quantum mechanics and Erwin Schrö dinger was the reason of
establishing an equation that considered as one of the fundamentals of quantum
mechanics (Freiberger, 2012).
There are two forms of the Schrodinger equation, the first form is time
dependent Schrö dinger equation and the second form is time independent
Schrö dinger equation (The Schrodinger Wave Equation, n.d.).

2.1 Time dependent Schrödinger wave equation:

∂
iℏ ψ=H−ψ (1.5)
∂t

δ
Where i is the imaginary unit, ℏ is the modified Planck’s constant (ℏ=h/2 π ),
δt
ψ
indicates a partial derivative with respect to time t, is the wave function of the
quantum system, and H ¿ is the Hamiltonian operator (Wikipedia, 2014).

iℏ
∂
∂t
ψ ( r , t )= [
−ℏ2 2
2m ]
∇ +V ( r ,t ) ψ (r , t) (1.6)

Where m is the mass of particle, V is the potential energy and ∇ 2 is the Laplacian.
The equation (1.5) is the general equation, while the equation (1.6) is the “single
non-relativistic particle” of the time dependent Schrö dinger equation. By solving
time dependent Schrö dinger equation, we can determine the probability of
detection of particle in some region as a function of time (Phillips, 2003).
2.2 Time independent Schrödinger wave equation:

Time independent Schrodinger equation is used more than time dependent

Schrodinger equation, because the time is measured on a small scale. “The time-
independent Schrö dinger equation predicts that wave functions can form
standing waves, called stationary states” (Wikipedia, 2014). The time
independent Schrö dinger equation has another important use that is making the
time dependent Schrö dinger equation to be solved easily once the stationary
states are predicated by the time independent Schrö dinger equation (Phillips,
2003).
Eψ¿ H ¿ ψ (1.7)

E ψ ( r )= [ −ℏ2 2
2m ]
∇ +V ( r ) ψ (r ) (1.8)
The equation (1.7) is the general equation, while the equation (1.8) is the “single
non-relativistic particle” of time independent Schrö dinger equation.

3. The Role of Quantum Mechanics in Structure-Based Drug Design

Over many decades, specialists used the high technological abilities to displace
the hard obstructions that they faced along the path of drug discovery.
This allowed them to improve the methods of drug design (Kalyaanamoorthy
and Chen, 2011). There were many computational approaches that used at
different stages of drug design process. These computational approaches were
successful in decreasing the number of ligands (“a molecule such as drug that
binds to receptor” (Dictionary.com, 2014).) In addition, in form the
computational approaches helped in reducing the period and costs of drug
discovery.
The computational approach that we will discuss about is the structure-based
drug design (SBDD). It is a method that depends on 3-D structures of biological
targets. SBDD has two phases; hit identification and lead identification. The first
phase is about exhibiting powerfulness against the target by the recognition of
chemical compounds called “hits”. “Whereas, the latter engages evaluation of the
screened hits to identify the promising lead molecules before proceeding toward
a large-scale lead optimization”(Kalyaanamoorthy and Chen, 2011). On of the
most successful examples of the history of SBDD is the development of human
immunodeficiency virus (HIV) proteinase inhibitor (Meyer and Swanson et al.,
n.p.).

3.1 Target Identification

Identifying the right target is only the first stage of a long process. Scientists need
to find a protein or gene that is associated with the disease (Kalyaanamoorthy
and Chen, 2011). Proteins come from genes, and it is easier to study genes than
to study proteins. One approach to find a new drug target, involves comparing
the genes of healthy individuals with those of people with the disease. The
differences between two genetics maps can help to generate hypotheses in which
proteins or lack of thereof cause the disease. It is also possible to do the opposite,
by changing one gene at a time in cells or simple organisms, and then observing
the resulting effects that will happen, so it called the phenotype of the mutation.
If the phenotype has some similarity with the disease’s states, it can give ideas
about the possible relation between the mutated gene and the disease. The third
approach of target identification is to start already with a bioactive substance
such as a natural medicine used in traditional medicine, a compound from basic
research or known drugs with unexpected effects (Kalyaanamoorthy and Chen,
2011).
When targets are identified they, another process occurs which called drug
validation. Drug validation is on of the most important steps in SBDD; many
drugs that failed were because it was not checked by “drug validation process”
(Hughes and Rees et al., 2011). When the target and the active site have been
identified then the hit discovery process starts. One of the successful validation
tools is the transgenic animal (animals that carry foreign genes) as they allow
observing the phenotypic endpoints (Hughes and Rees et al., 2011).
3.3 Hit to Lead Phase

“Hit to lead” phase is an elevated level of SBDD phases. It helps pharmaceuticals

to get closer to a drug that is safe and efficacious in people because it helps to
identify compounds with improved potency (Hughes and Rees et al., 2011).
“A lead compound is a compound that demonstrate a desired a biological activity
on a validated molecular target” (Pharmacelsus GmbH, 2013). The key thing
about the hit to lead phase is to identify compounds that is not only binds to the
protein, but they in fact work inside a cell, and they show the selectivity in a cell
(Hughes and Rees et al., 2011). The key aspect of hit to lead stage is a repeated
process in which it not only shows that the compound works in a biochemical
assay, but it also demonstrate that it works effectively and selectively in a cell-
based assay (Hughes and Rees et al., 2011). Therefore, it can go through the cell
membrane, reach the target inside the cell, and engage that protein in a cell-
based assay. In starting the hit to lead phase, the compounds start off with
potencies that are weaker than pharmaceuticals would like. What
pharmaceuticals looking for is compounds that will make the medicinal
chemistry that will improve the potency of the hit compound at least a factor of
ten, and ideally a factor of twenty in the biochemical assay (Kalyaanamoorthy
and Chen, 2011). Also, pharmaceuticals look for things to start off with from the
hit stage that have weak cellular potency, but with medicinal chemistry that
correlates with the biochemical potency mentioned above (Kalyaanamoorthy
and Chen, 2011). Furthermore, it drives the cellular potency to be more potent in
the cell. This is all toward the goal that pharmaceuticals want to get potent
compounds that are cell active.
4. Quantitative Structure-Activity Relationship (QSAR)

The quantitative structure-activity relationship (QSAR) is considered as one of

the earliest approaches to drug design. This approach is all about finding a
relationship between how active the compound is as a drug and the physical
activities of the compound. The fundamental principle of QSAR is that the
change in structural properties of the compound can lead to a change in the
biological activities of the compound. QSAR allowed us to determine where
approximately the drug settles in the human body. This is determined by a
physical property that used which called the distribution coefficients between
octanol and water (is the ratio between the concentration of a compound in the
mixture). “QSAR depends on bulk properties of the potential drug molecules”
(Moore, 2002). A new method is emerged, it is called 3D-QSAR, 3D-QSAR is
considered to be an effective tool in the design of pharmaceuticals drugs that
helps to connect the activity of a molecule with the properties that depends on a
special part of the molecular structure. We superimpose by a computer a set of
molecules that we know their activities. By this method, the set of molecules with
similar groups will be in the same place. Furthermore, a small box is drowned
that divided into lattice of n points along each side and 200pm apart from each
other (Moore, 2002). The box contains all the molecules. A box containing one
molecule is shown in figure 2.0