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Biophysics in the Understanding, Diagnosis, and Treatment of Infectious Diseases Poster Abstracts
52
9-POS
Board 9
Multiscale Simulation to Understand the Bactericidal Action of the AS-48 Antimicrobial
Peptide
Victor Cruz
, Javier Ramos, Javier Martinez-Salazar.
IEM-CSIC, Madrid, Spain.
The AS-48 bacteriocin is a cyclic peptide with selective antimicrobial activity towards Gramm-
positive and Gramm-negative bacteria[1].
Although the structure of the peptide has been elucidated by NMR[2] and X-ray
crystallography[3], little is known about the precise mechanism of action. Some electroporation
data suggest that the peptide is able to promote pore formation in bacterial membranes[4].
We performed Molecular Dynamics simulations at atomistic and coarse-grained scales to study
the structural characteristics of AS-48 and its interaction with different lipid bilayers. The Force
Fields used were Gromos 53A6 for the atomistic resolution and Martini[5] for the mesoscale
representation.
Previous work on self-assembling simulations had revealed the ability of the amphoteric
bacteriocin to promote two kinds of pores with different size[6].
The results show that AS-48 preferentially binds bilayers composed by anionic rather than
zwitterionic lipids, as is the case for bacterial membranes.
In summary, the simulation protocols help to understand the mechanistic implications of the AS-
48 bioactivity and will be able, for example, to propose mutations that could improve the AS-48
antimicrobial action.
1. Sanchez-Hidalgo, M.; Montalban-Lopez, M.; Cebrian, R.; Valdivia, E.; Martinez-Bueno, M.;
Maqueda, M. Cell Mol Life Sci 2011, 68(17), 2845-2857.
2. Gonzalez, C.; Langdon, G. M.; Bruix, M.; Galvez, A.; Valdivia, E.; Maqueda, M.; Rico, M.
Proc Natl Acad Sci USA 2000, 97(21), 11221-11226.
3. Sanchez-Barrena, M. J.; Martinez-Ripoll, M.; Galvez, A.; Valdivia, E.; Maqueda, M.; Cruz,
V.; Albert, A. J Mol Biol 2003, 334(3), 541-549.
4. Galvez, A.; Maqueda, M.; Martinezbueno, M.; Valdivia, E. J Bacteriol 1991, 173(2), 886-892.
5. Monticelli, L.; Kandasamy, S. K.; Periole, X.; Larson, R. G.; Tieleman, D. P.; Marrink, S.-J. J
Chem Theor Comput 2008, 4(5), 819-834.
6. Cruz,V.L.; Ramos J.; Melo,M.N.; Martinez-Salazar J. BBA-Biomembranes
2013,1828(11),2524-2531