PROCEEDINGS OF THE INTERNATIONAL CONFERENCE

NANOMATERIALS: APPLICATIONS AND PROPERTIES

Vol. 2 No 4, 04NABM11(6pp) (2013)

Computational Study of Amino Acids, Order to Simulation of Membrane Protein Channels

Using by Theoretical Methods
Reza Rasoolzadeh*
Young Researchers Club and Elites, Science and Research Branch, Islamic Azad University, Tehran, Iran
(Received 02 June 2013; revised manuscript received 02 August 2013; published online 31 August 2013)
The importance of ionic channels is due to the passage of ions across the cell membrane which is based
on electrochemical gradients. The structure of ionic channels often includes one or several central cores
which makes up the pore. The direct electron transfer between the enzyme and unmodified electrode is
usually prohibited due to shielding of the redox active sites by the protein shells. In this paper, we have
studies the stability of C60-amino acids clusters using by semi-empirical method and investigation of vibrational frequencies and electrical properties.
Keywords: Membranes proteins- membrane channels-, Amino acids- semi empirical.
PACS numbers: 87.15.kr, 87.15.ap

INTRODUCTION
Protein helices which make up the pore have consisted of four distinct subunits or one subunit which includes repetitive parts. Any disorder in protein-made
channels causes paroxysm attacks. For instance, we can
mention neuromuscular diseases as one type of these
illnesses. These diseases are called disorders of ionic
canals.
The function of channels is to allow selectivity and
specificity for a Variety of molecular species transport
across the cell membrane [1-4]. These channels, included: a) ligand-gated channels, b) voltage-gated channels,
c) second messenger gated channels, d)mechanosensitive
channels, e) Gap jucnctions: porins not gated [5-6].
The first step in understanding the physical mechanism of potassium transport through this protein nanopore is the determination of the water molecular distribution along the axial length of the pore Ion channels
which are membrane proteins that mediation flux between the outside of the cell through a small, water-filled
hole in the membrane-a pore. Ion- Selective pores were
originally proposed to explain separate Components of
Na+, K+ and leak currents in the classic experiments of
Hodgkin and Huxley [7]. Potassium channels are the
most diverse group of the ion channel family[1]. The recent determination of the crystallographic structure a
bacterial K+ channel from streptomyces lividans (KcsA)
[2] has provided the moleculer basic for understanding
the physical mechanisms Controling ionic selectivity ,
permeation, and transport through Various types of K+
channels. [3-4].
In all cases, the functional K+ channel is tetramer [5],
typically of four identical Subunits folded around a central Port [2]. Voltage gated potassium (Kv) channels
are members of the voltage gated ion channel superfamily [1-2], which is important for initation and propagation of action potentials in excitable cells. They are
composed of four identical or homologous Subunits, each
containing six transmembrane segments: S1-S6. Segments: S1-S4 form the voltage- sensing domain (VSD),
and segments S5 and S6 Connected by the P loop, which
*

is involved in ion selectivity, Comprise the pore- forming

domain (PD) S4 has four gating charge- carrying arginines (R1-R4) spaced at intervals of three amino acid
residues, which are highly conserved and are thought to
play a key role in coupling changes in membrane Voltage
to opening and closing of the pore [3-5]. In the Kv channels 13 electronic charges across the membrane electrical field per channel between the closed and open states
[6-8]. Arginine residues interacting with lipid phosphate
groups play an important role in stabilizing the voltageSensor domain of the KvAP channel within a bilayer.
Simulations of the bacterial potassium channel kcsA
reveal specific interactions of phosphatidylglycerol with
an acidic lipid-binding site an the interface between adjacent protein monomers. Molecular and langevin dynamics simulation as well as Monte Carlo simulation
have been used to investigate protein folding pathways
with some success. The metropolis Monte Carlo was originally developed for calculating equilibrium properties of
physical systems [9-12].The metropolis algorithm performs a sample of the configuration space of system
starting from a random conformation and repeating a
large number of steps. Molecular dynamics simulation is
one the most promising approaches for solving the protein folding problem in this method we observe the time
behavior of atoms of the system in MD simulation, new
positions of atoms are calculated by numerical integration of newton's equation of motion [13-16].
The repentance of the existence of buckminsterfullerene C60 [17], theoretical speculation about carbon clusters
[18] over 36 years was finally verified. Since then, this
beautiful molecule has attracted ever more attention of
theoretical and experimental scientists. Some chemists
began to focus their research on the chemistry of this molecule, but real fullerene chemistry began only after 1990
when Kratschmer et al. described a method for preparing
macroscopic quantities of C60 [19].
Direct electron transfer between the electrode and
the redox enzyme is very important for fundamental
studies and construction of biosensors [20-22]. However,
the direct electron transfer between the enzyme and
unmodified electrode is usually prohibited due to shield-

[email protected]

2304-1862/2013/2(4)04NABM11(6)

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2013 Sumy State University

REZA RASOOLZADEH

PROC. NAP 2, 04NABM11 (2013)

ing of the redox active sites by the protein shells [23, 24].
Therefore, several studies have been made to enhance
the electron transfer. Mediators are widely used to access the redox center of an enzyme and then to act as the
charge carriers. Mediators can minimize the effects of
interferences, lower the operating potential of the electrodes, and improve the linear response range and sensitivity of the sensor [25]. Use of carbon nanotubes (CNTs)
as mediators has attracted increasing attention in recent
years. Comparing with traditional carbon electrodes,
CNTs show unique properties, such as good conductivity,
high chemical stability, and catalytic activities towards
many electrochemical reactions [24, 26, 21, 27, 28]. More
importantly, it is possible to bring the nanotubes close to
the redox centers of the proteins [29, 30].

rors than AM1, are sufficient to study carbon systems,

mainly for the enthalpies of formation [37].
All calculations presented here were performed with
semi-empirical Molecular mechanics (MM+) (Table 2).
In the first step of the calculations we optimized the
geometry and defined Potential Energy of the nanotube
structure by performing molecular mechanics calculation
using MM+ force field, if too large a time step is used in
monte carlo simulation, it is possible to have a basic instability in the equations that result in a molecule blowing apart, we need small time steps to preserve integration accuracy, however in the monte carlo time step
50 femtoseconds (0.05 ps) was appropriate.
In the next step we calculated the Vibrational modes
of the tube by applying the semi-empirical molecular orbital method by the Hyperchem-7 package program [39].

THEORETICAL BACKGROUND AND

COMPUTATIONAL METHODS

RESULTS AND DISCUSSION

Many studies have shown that the carbon nanotubes

possess remarkable mechanical and physical properties
leading to many potential applications such as fluid
transport, fluid storage at nanoscale, and nanodevices
for drug delivery Since controlled experiments at the
nanometer scale are very difficult, the simulation techniques have been widely and successfully used to investigate the mechanical property, wave propagation and
resonant frequency [31]. The vibration of molecules is
best described using a quantum mechanical approach. A
harmonic oscillator does not exactly describe molecular
vibrations. Bond stretching is better described by a
Morse potential and conformational changes have sinewave-type behavior. However, the harmonic oscillator
description is very useful as an approximate treatment
for low vibrational quantum numbers [32]. A harmonic
oscillator approximation is most widely used for computing molecular vibrational frequencies because more
accurate methods require very large amounts of CPU
time. Frequencies computed with the Hartree-Fock approximation and a quantum harmonic oscillator approximation tends to be 10 % too high due to the harmonic
oscillator approximation and lack of electron correlation
[33]. The high-frequency oscillations encountered using
flexible water models are of the order of 3500 cm 1
which are somewhat larger than the CNT vibrational
modes of 1500 cm 1 [34]. Hence, for this case study, the
use of the flexible water and solvent model.
Vibrational frequencies from semi-empirical calculations tend to be qualitative in (which) they reproduce the
general trend mentioned in the Results here. However,
the actual values are erratic. Some values will be close,
whereas others are often too high. However PM3 is generally more accurate than AM1.
Since periodic boundary conditions cannot be adopted, first principles calculations of finite-length SWCNTs
are only affordable to relatively small systems with C
atom number less than 300 within our present computational ability [35].
The molecular mechanics method using the MM+
force field, and the Austin Model 1 (AM1) [36] and Parameterized Model number 3 (PM3) [37] semi-empirical
method within the Restricted Hartree-Fock (RHF) formalism are sufficient to study carbon systems [38]. In
1989, Stewart improved the techniques of parameterization and published PM3, which gave lower average er-

The resulting method was denoted, and in a sense, it

is the best set of parameters (or at least a good local minimum) for the given set of experimental data. The optimization process, however, still requires some human
intervention in selecting the experimental data and assigning appropriate weight factors to each set of data.
As a reference Table 1 is the result of semi-empirical
computation using both method AM1& PM3.
At the first glance in Table 1, it can be observed by
increasing dielectrics, normal modes will move to upper
normal modes ratio and Vibrational frequencies resulted
from semi-empirical Calculations tend to be qualitative.
Therefore by increasing dielectric the higher frequency will be gained in which semi-empirical methods will
have the same operating procedure.
The PM3 and AM1 methods are also more popular
than other semi-empirical methods due to the availability of algorithms for including salvation effects in these
calculations. There are also some known strengths and
limitations of PM3. Overall heats of formation are more
accurate than with AM1. Hypervalent molecules are also
predicted more accurately. On average, PM3 predicts
energies more accurately than AM1.
The heats of formation are more accurate than AM1
or PM3 depending on the nature of the system and information desired, they will often give the most accurate
obtainable results for organic molecules with semiempirical methods. On average, PM3 predicts energies
and geometries better than AM1.
There is energy of interaction in between solvent and
solute. Therefore, the solute properties dependent on
energy, such as geometry, total energy and vibrational
frequencies depend on the solvent. The presence of a
solvent, particularly a polar solvent, can also stabilize
charge separation within the molecule. This not only
changes the energy, but also results in a shift in the electron density and associated properties. In reality, these
are the result of the quantum mechanical interaction
between solvent and solute, which must be averaged
over all possible attitudes of solvent molecules consistent
with the principles of statistical mechanics. The results
of the C60-aminoacids clusters simulation can be used
to analyze the energetic aspects which are associated
with the process of introducing a C60 fullerene from the
gas phase into different amino acids ( Table 2 and
Fig. 1).

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COMPUTATIONAL STUDY OF AMINO ACIDS

PROC. NAP 2, 04NABM11 (2013)

Table 1 Calculated Properties of C60 and binding to amino acids

Atom
numb
er
1
2
3
4
5
14
56
66
67
68
69

Normal
mode
Max

C60 Ala gly

C60 Ala leu

C60 Gln asn

Atomic
number

18.293
14.653
14.621
22.238
14.714
14.744
14.657
18.404
14.735
14.690
22.367

6.77
7.79
9.10
9.32

0.446
0.107
0.337
0.285
0.413
0.207
0.027
0.406
0.240
0.358
0.429

1
2
3
4
5
6
7
8
9
15
69

18.301
14.673
14.651
22.260
14.765
14.683
14.776
18.382
14.714
14.729
22.364

70

14.743

0.231

70

18.412

9.61

0.423

71

14.735

0.133

71

14.726

8.39

0.136

72

14.771

0.389

72

14.714

7.20

0.175

73

14.756

0.395

73

22.346

7.53

0.320

74

14.728

8.61

0.344

75

14.619

7.57

0.561

76

22.335

6.55

0.470

77

18.309

8.02

0.711

B
7.85
9.85
7.85
5.48
8.94

Atom
number

0.393
0.188
0.322
0.310
0.399
0.135
0.172
0.368
0.116
0.3 62
0.452

1
2
3
4
5
6
7
8
9
15
69

18.264
14.664
14.666
22.257
14.728
14.733
14.733
22.361
18.329
14.776
14.649

6.30
7.53
6.68
8.71
9.94
11.19
11.23
12.34
6.32
5.53

0.469
0.047
0.339
0.386
0.236
0.351
0.513
0.453
0.718
0.020
0.101

Frequency

Intensity

Frequency

Intensity

Frequency

Intensity

225 A

1A

261 A

6A

267 A

1A

2819.29

2971.76

2811.35

2151.43

3056.54

751.13

2739.14

2895.54

3154.71

Dipole
moment

11.7590

3.2852

14.0020

Table 2 Semi empirical Calculations for C60 fullerene and conjunction to amino acids
Atom
number
1
2
5
6
9
10
51
52
55
56
59
60
Normal
mode
Max
E
Dipole
moment

A
14.562
14.562
14.559
14.560
14.56
14.560
14.567
14.568
14.592
14.588
14.604
14.607

C60 Nanotube
B
5.91621
5.91621
5.91623
5.91621
5.91624
5.91625
5.91618
5.91619
5.91619
5.91617
5.91634
5.91634

Frequency
71 AU
1363.12

C
0.049
0.050
0.053
0.051
0.052
0.052
0.068
0.061
0.040
0.045
0.022
0.025
Intensity
2A
457.69

2283.99
4.1475

04NABM11-3

REZA RASOOLZADEH

PROC. NAP 2, 04NABM11 (2013)

Fig. 1 Plotting of Calculated Properties of C60 and binding to amino acids

04NABM11-4

COMPUTATIONAL STUDY OF AMINO ACIDS

PROC. NAP 2, 04NABM11 (2013)

The net result clearly indicates that the process of introducing a C60 to different amino acids energetically is
remarkable.
Whereas a molecular mechanics potential used to
characterize the response of a SWCNT which allows long
range interactions between atoms, results in Molecular
Mechanics force field which indicates that potential energy is maximum and also the potential energy will increase. (As shown in Table 2 and Fig. 1).
CONCLUSION
To reconstruct membranos proteins, we used simulated nanotubes in order to transfer ions across the
membrane and transfer of ions was done successfully. In
this study the more the potential energy increases the
more the conductivity of nanochannels decreases and we
chose the least energy among nanotube and amino acid

complexes. And also the more energy we use, the more

conductivity we will have; therefore we choose the complex which conducts the most current. This way we can
simulate the channels which have hereditary defects and
are not efficient and observe the fundamental cure of the
diseases.
According to the Conference policy, the proceedings
will be published instead of the abstract book. The conference proceedings will be published up to the conference sessions for the convenience of the participants
and the best dissemination through the Web, since the
proceedings paper will be freely available on-line. In
order to speed up the availability of your paper online,
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preparation exist.

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04NABM11-5

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PROC. NAP 2, 04NABM11 (2013)

Notes: (A) Electric Potential, (B) Electrostatic Properties, (C) Total atomic charges
Atom
Number
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
19
73

Normal
mode
Max

C60 His-Pro
A
18.421
14.757
14.713
22.380
14.800
14.798
14.769
18.322
14.690
14.702
22.316
14.694
14.619
18.192
14.633
14.564
18.187
14.698
14.774

B
10.12
8.93
7.67
7.92
9.29
10.82
11.22
6.66
7.78
9.04
9.14
8.25
9.55
10.31
10.36
11.42
11.46
5.48
6.36

C
0.502
0.054
0.321
0.414
0.253
0.276
0.140
0.608
0.063
0.182
0.392
0.288
0.276
0.679
0.149
0.411
0.679
0.186
0.217

C60 Lys-Arg

Atom ic
number
1
2
3
4
5
6
7
8
9
10
11
17
70
72
73
74
75
76
77

A
18.340
14.753
14.769
22.375
14.751
14.732
14.652
18.228
14.496
18.215
18.218
14.771
14.761
18.513
14.797
14.728
22.350
14.795
14.778

B
6.28
7.43
7.96
7.54
8.66
9.86
11.10
12.30
13.51
13.80
14.54
6.44
5.38
9.18
8.59
7.48
7.22
9.74
9.46

C
0.593
0.065
0.178
0.398
0.255
0.282
0.120
0.649
0.863
0.728
0.741
0.159
0.052
0.514
0.123
0.371
0.447
0.236
0.234

78

14.718

10.81

0.271

79
80

14.637
18.155

10.84
12.24

0.207
0.680

Frequency

Intensity

Frequency

Intensity

273 A

1A

1A

2A

250285.34

6967.70

2997.06

E
Dipole
moment

776150.43

3082.21

3235.42

32.3063

33.2251

Notes: (A) Electric Potential, (B) Electrostatic Properties, (C) Total atomic charges
Atom
number
1
2
3
4
5
6
8
61
67
68
69
70
71
72
73
Normal mode
Max
E
Dipole
moment

A
18.30
14.67
14.64
22.23
14.67
22.31
14.71
14.69
18.42
14.70
14.68
22.30
14.64
22.17
14.74

C60 Ser-Thr
B
7.14
8.09
8.44
7.99
9.46
10.44
5.85
5.97
8.89
8.05
6.94
6.94
7.63
6.91
8.989

Frequency
1A
13398.17

C
0.50
0.10
0.36
0.25
0.01
0.59
0.30
0.03
0.46
0.12
0.04
0.34
0.03
0.47
0.38

Atomic
number

Intensity
2A
256602636550144
2967.73
6.7668

1
2
3
4
5
6
7
13
66
68
69
70
71
72

A
18.28
14.65
14.64
22.25
14.71
14.73
14.74
14.69
14.73
18.39
14.72
14.69
22.35
14.77

C60 Val-Ala
B
6.52
7.76
8.55
8.26
8.78
9.20
10.07
5.52
6.28
8.64
7.89
7.51
7.89
8.95

Frequency
1A
15771.21

Intensity
27 A
57292804325376
2857.42
8.2113

04NABM11-6

C
0.25
0.02
0.33
0.33
0.12
0.42
0.40
0.24
0.10
0.63
0.11
0.31
0.40
0.37