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Biophysics of Proteins at Surfaces: Assembly, Activation, Signaling
Poster Abstracts
13-POS
Board 13
Coarse Graining to Investigate Membrane Induced Peptide Folding of Anticancer Peptides
Sai Janani Ganesan
1
, Hongcheng Xu
3
, Joel Schneider
2
, Robert Blumenthal
2
, Silvina
Matysiak
1,3
.
1
University of Maryland, College Park, College Park, MD, USA,
2
National Cancer Insitute,
Frederick, MD, USA,
3
University of Maryland, College Park, College Park, MD, USA.
Information about membrane induced protein folding mechanisms using all-atom molecular
dynamics simulations is a challenge due to time and length scale issues. On the same hand,
coarse-grained (CG) modeling has made a significant impact on our understanding of multiple
processes, from self assembly of lipid bilayers to amyloid-fibril formation. However, there is a
lack of a low resolution, transferable model to study mechanisms of peptide folding in a
membranous environment. We recently developed a low resolution Water Explicit Polarizable
PROtein coarse-grained Model (WEPPROM) by adding oppositely charged dummy particles
inside protein backbone beads. These two dummy particles represent a fluctuating dipole, thus
introducing introducing structural polarization into the coarse-grained model. With this model,
we were able to achieve significant
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/
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secondary structure content de novo, without any added
bias. We extended the model to zwitterionic and anionic lipids, by adding oppositely charged
dummy particles inside polar beads, to capture the ability of the head group region to form
hydrogen bonds. Our models have their roots in the MARTINI force field. We use zwitterionic
POPC (Palmitoyl Oleoyl Phosphatidyl Choline) and anionic POPS (Palmi- toyl Oleoyl
Phosphatidyl Serine) as our model lipids, and a cationic antimicrobial peptide with anticancer
activity, SVS1, as our model peptide. In this work, we characterize the driving forces for SVS1
folding on lipid bilayers with varying anionic and zwitterionic lipid compositions. We use SVS1
mutants that do not fold as our negative peptide control. Peptides are used as model systems to
understand protein behaviour. Based on our results, membrane induced peptide folding is driven
by both (a) cooperativity in peptide self interaction and (b) cooperativity in membrane-peptide
interaction. This work compares and contrasts the relationship between lipid composition and its
role in peptide folding.