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INTERACTION OF L-ALANINE AND L-VALINE AMINOACID MOLECULES

WITH PHOSPHOLIPID BILAYER.


MOLECULAR DYNAMICS SIMULATION

S. A. Aramyan , A. H. Poghosyan ,
Cor. Member of NAS RA A. A. Shahinyan

Institute of Applied Problems of Physics of National Academy of Sciences of


Armenia,
Hr. Nersisian 25, 0014, Yerevan, Republic of Armenia; Tel.: (+374 10) 245 896; e-
mail: sona_aramyan@yahoo.com;

International Scientific and Educational Center of National Academy of Sciences


of Armenia,
Marshal Baghramian Ave. 24d, 0019 Yerevan, Republic of Armenia; Tel.: (+374
10) 583 691
ABSTRACT

It is well known the importance of investigations of interactions between


proteins and phospholipid bilayers. We decided to give a deeper sight to this
problem by the determination of ways of interactions between aminoacids
and phospholipid bilayers using computer simulation methods. By means of
simulation, remarkable progress is being made in the understanding of
protein folding, lipid bilayer behavior and peptide-lipid interactions. There
were used the molecules of L-alanine and L-valine and phospholipids bilayer
consisting of 128 Dipalmitoylphosphatidylcholine (dppc) molecules and 3655
water molecules, which corresponds to fully hydrated state of dppc bilayer.
For the computer experiment the GROMACS simulation package and
GROMOS force fields were used. There were done two main simulations of
systems containing L-ala and bilayer and correspondingly L-val and bilayer.
Both simulations were done with the duration of 15 ns and under the same
conditions with same parameters.
INTRODUCTION
During last decades the accumulation of biological information is continuing,
besides this during last years it is accumulating in forms of electronic versions,
such as texts, images and so on. Because of the presence of this huge amount of
information is rising a problem of systematization and adequate usage of this
amount of experimental data.

Bioinformatical methods give an appropriate salvation to these problems. Besides


systematization, during last decade, it gives an opportunity to make models and
investigate complex biological and chemical molecules and processes.

The aim of this work was to determine the ways of interaction of aminoacids with
phospholipid bilayers using computer simulation methods. Particularly for these
simulations the method of molecular dynamics was used. It was interesting to
find out in details the ways of aminoacid-phospholipids bilayer interactions in
atomic scale. There were used molecules of L-alanine and L-valine with the bilayer
consisting of 128 dipalmitoilphosphatidilcholine (dppc) and 3655 water molecules.
In this experiment there are elucidated many nuances of aminoacid behavior and
bilayer property changes during aminoacid addition to bilayer.
METHODS

The molecular dynamics simulations were carried out using GROMACS


simulation package (version 3.2.1, single
precision) [4]. Simulations were performed on Armcluster, which was
founded in Institute of Informatics and
Automatization Problems of NAS RA by ISTC A-823 project. The VMD
package [5] was used for visualization and molecular graphics.
The interactions between, L-valine/bilayer, L-alanine/bilayer were
examined. There were investigated two systems consisting of L-alanine, and
L-valine molecules and phospholipid bilayers (128 DPPC and 3655 water
molecules, which corresponds to fully hydrated state of phospholipid
bilayer) (Fig. 1). For the system preparation water was removed
from bilayer and then the aminoacid molecule was added right onto the
bilayer surface. After aminoacid addition water
was palced back onto its starting configuration.
BILAYER PROPERTIES

For the description of bilayer properties there were


measured some parameters such as area per lipid
and bilayer thickness. In most of cases
measurements were done on the nearest to
aminoacid part of bilayer. On Fig. 2 you can see
changes of area per lipid (on the aminoacid
neighboring part of bilayer) during simulation time.
From the real physical experiment this value was
received as 0.62 nm2 [14]. As you can see this
value is decreasing up to approximately 0.4 nm2.
This means that lipids are getting closer to each
other after aminoacid addition. On Fig. 3 are
presented the changes of bilayer thickness
measured as a distance between aminoacid
neighboring lipid headgroup phosphorus of upper
and lower layers.
This value from real experiment was 3.7 nm
but you can see that thickness is decreasing
too during simulation to ~3.5 nm [14].
There were also measured total energies of
bilayers (Fig.4). From this value we can see
whether system is stable or not. As you can see
after 1.5 ns system stabilizes and there are
little changes in energy after this time.

Aminoacid behavior
In Fig. 5 you can see the permeation of
aminoacid into the bilayer. During simulation
aminoacids are entering to bilayer from their
starting point until phosphorus level (7.5 ns)
and then even go deeper then average
phosphors. From figure it is clear that at the
end of simulation, starting from 12 ns till end,
L-valine penetrates deeper then L-alanine,
which can be explained by L-valines more
hydrophobicity compared with L-alanine.
CONCLUSIONS

• In conclusion we can say that we have modeled for the first time
the above mentioned aspect of interaction between phospholipid
bilayer and aminoacids.
• Several parameters, describing the structure of the bilayer, such as
area per lipid on the surface of bilayer, thickness of bilayer,
arrangement of aminoacid molecules in the bilayer were
investigated.
• We have got that areas per lipid for the aminoacid neighboring part
of bilayer are decreasing from 0.62 to 0.4 nm2. And the bilayers
thicknesses again for the aminoacid neighboring part of bilayers are
decreasing from 3.7 to 3.5 nm.
• Aminoacids center of masses are penetrating into the bilayer
deeper then lipids average phosphorus for 0.3 nm, furthermore L-
valine is penetrating deeper than L-alanine.
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