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