title: Interplay between the hydrophobic effect and dipole interactions in peptide aggregation at interfaces.
abstract: Protein misfolding is an intrinsic property of polypeptides, and misfolded conformations have a propensity to aggregate. In the past decade, the development of various coarse-grained models for proteins has provided key insights into the driving forces in folding and aggregation. We recently developed a low resolution Water Explicit Polarizable PROtein coarse-grained Model (WEPPROM) by adding oppositely charged dummy particles inside protein backbone beads. With this model, we were able to achieve significant α/β secondary structure content, without any added bias. We now extend the model to study peptide aggregation at hydrophobic-hydrophilic interfaces and draw comparisons to aggregation in explicit water solvent. Elastin-like octapeptides (GV)4 are used as a model system for this study. A condensation-ordering mechanism of aggregation is observed in water. Our results suggest that backbone interpeptide dipolar interactions, not hydrophobicity, plays a more significant role in fibril-like peptide aggregation. We observe a cooperative effect in hydrogen bonding or dipolar interactions, with an increase in aggregate size in water and at interfaces. Based on this cooperative effect, we provide a potential explanation for the observed nucleus size in peptide aggregation pathways. The presence of a hydrophobic-hydrophilic interface increases both (a) order of aggregates formed, and (b) rate of the aggregation process. Without dipolar particles, peptide aggregation is not observed at the hydrophilic-hydrophobic interface. Thus, the presence of dipoles, not hydrophobicity, plays a key role in aggregation observed at hydrophobic interfaces.
authors.affiliation: Fischell Department of Bioengineering, University of Maryland, College Park, Maryland, USA.
authors.forename: Sai J
authors.initials: SJ
authors.lastname: Ganesan
authors.affiliation: Fischell Department of Bioengineering and Biophysics Program, University of Maryland, College Park, Maryland, USA. matysiak@umd.edu.
authors.forename: Silvina
authors.initials: S
authors.lastname: Matysiak
mesh_terms: D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D010455:Peptides / Q000737:chemistry*; D014867:Water / Q000737:chemistry
chemical_list: D010455:Peptides; D014867:Water