posted on 2024-02-17, 14:05authored byTania Rajpersaud, Sara Tabandeh, Lorraine Leon, Sharon M. Loverde
Polyelectrolyte
complexes (PECs) are currently of great interest
due to their applications toward developing new adaptive materials
and their relevance in membraneless organelles. These complexes emerge
during phase separation when oppositely charged polymers are mixed
in aqueous media. Peptide-based PECs are particularly useful toward
developing new drug delivery methods due to their inherent biocompatibility.
The underlying peptide sequence can be tuned to optimize specific
material properties of the complex, such as interfacial tension and
viscosity. Given their applicability, it would be advantageous to
understand the underlying sequence-dependent phase behavior of oppositely
charged peptides. Here, we report microsecond molecular dynamic simulations
to characterize the effect of hydrophobicity on the sequence-dependent
peptide conformation for model polypeptide sequences that were previously
reported by Tabandeh et al. These sequences are designed
with alternating chirality of the peptide backbone. We present microsecond
simulations of six oppositely charged peptide pairs, characterizing
the sequence-dependent effect on peptide size, degree of hydrogen
bonding, secondary structure, and conformation. This analysis recapitulates
sensible trends in peptide conformation and degree of hydrogen bonding,
consistent with experimentally reported results. Ramachandran plots
reveal that backbone conformation at the single amino acid level is
highly influenced by the neighboring sequence in the chain. These
results give insight into how subtle changes in hydrophobic side chain
size and chirality influence the strength of hydrogen bonding between
the chains and, ultimately, the secondary structure. Furthermore,
principal component analysis reveals that the minimum energy structures
may be subtly modulated by the underlying sequence.