Short surfactant-like amphiphilic
peptide, A3K, resembling
a surfactant with a hydrophobic tail (A3) and a polar headgroup
(K), is experimentally determined to form a membrane. Although the
peptides are known to exist as β-strands, the exact packing
architecture stabilizing the membrane is unknown. Earlier simulation
studies have reported successful packing configurations through trial
and error. In this work, we present a systematic protocol to identify
the best peptide configurations for different packing patterns. The
influence of stacking peptides in square and hexagonal packing geometry
with the neighboring peptides in parallel and antiparallel orientations
was explored. The best peptide configurations were determined from
the free energy of bringing 2–4 peptides together as a bundle
that can be stacked into a membrane. The stability of the assembled
bilayer membrane was further investigated through molecular dynamics
simulation. The role of peptide tilting, interpeptide distance, the
nature and the extent of interactions, and the conformational degrees
of freedom on the stability of the membrane is discussed. The consistency
with the experimental findings suggests hexagonal antiparallel as
the most relevant molecular architecture.