THE EFFECT OF CYCLOTIDE ON
MEMBRANE CONFORMATION :
A MOLECULAR DYNAMICS
SIMULATION STUDY
ABSTRACT
Cyclotides are cyclic antimicrobial peptides that has promising features for the development of efficient pharmaceutical
therapies. It is believed that anti-bacterial activities may result from membrane disruption by the hydrophobic cyclotides.
Their efficacy is still hampered by lack of molecular details of their mechanism/mode of action. Therefore, current studies
has been under taken in order to predict the function and mode of molecular mechanism of action. Molecular dynamics
(MD) simulation was done using GROMACS to investigate the interactions between a representative cyclotide (vibi A) and
bilayers comprising 1palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE) lipids. The constructed simulation
system goes through neutralization, energy minimization and equilibration steps before undergoing 20 ns MD simulation
run. This study is attempt to understand any conformational changes on the cyclotide membrane interaction at different
temperatures (293K, 303K and 313K). The results were analysed in form of system properties, RMSD and RMSF to indicate
the molecular mechanism underlying protein-membrane interaction. As a conclusion, the research might help in setting up
model system for more advanced computation in the future.
METHODOLOGY
OBJECTIVES
construction of model system
1. To build a model
of membrane
embedded with
cyclotide.
2. To run
molecular
dynamics
simulations using
the above
mentioned model
system.
3. To analyze
simulation data
and deduce
possible
molecular
mechanism of
action.
energy minimization
molecular dynamics simulation
analysis of data
RESULTS
Figure 4.1 : RMSD analysis at
three different temperature
(293 K,303 K, 313K )
Figure 4.2 : RMSF analysis at
three different temperature
(293 K,303 K, 313K )
Model membrane system
before vibi A solvated in a
POPE membrane with water
in side view at 303K
CONCLUSIONS
1. Model system of POPE membrane and embedded vibi A cyclotide was constructed and run at
three different temperature 293K,303K and 313 K in 20 ns.
2. RMSD and RMSF result shows that conformational changes was observed at different
temperature in membrane environment.
Model membrane system
after vibi A solvated in a
POPE membrane with
water in side view at 303K
PROJECT DONE BY
Atieya binti Abdul Hadi
4 SQBI (industrial Biology)
Faculty of Biosciences and
Medical Engineering
REFERENCES
Burman, R. et al., 2011. Cyclotide-membrane interactions: defining factors of membrane binding, depletion and
disruption. Biochimica et biophysica acta, 1808(11), pp.2665–73.
Henriques, S.T. & Craik, D.J., 2010. Cyclotides as templates in drug design. Drug discovery today, 15(1-2), pp.57–
64.
RESEARCH POSTER PRESENTATION DESIGN © 2012
www.PosterPresentations.com
Dr. Mohammed Abu Naser
Faculty of Biosciences and
Medical Engineering