Does there exist an intrinsic relationship between the flexibility and self-assembly of pepfactants?

Abstract

Short peptide surfactants (pepfactants) bearing the amphiphilic molecular architecture of hydrophobic and hydrophilic moieties are attractive for a wide range of biological and medical applications. Understanding of structural basis and molecular mechanism underlying the self-assembling behaviour of pepfactants is fundamentally important for rationally designing surfactant-like peptides to function as diverse biomaterials. To date, however, the relationship between the physicochemical properties and self-assembly of pepfactants still remains largely unexplored. In this study, we attempt to elucidate the role of structural flexibility and dynamics in peptide self-assembly. Two fast and reliable quantitative structure–property relationship predictors are carefully developed with the sophisticated genetic algorithm/partial least squares method; the predictors are then applied to estimate molecular flexibility and self-assembling ability for 10,000 randomly generated surfactant-like peptides. As a result, a significant negative correlation between the flexibility and self-assembly is observed, which can be fitted fairly well using an exponential curve. Furthermore, atomistic molecular dynamics simulations also reveal a noticeable difference of flexibility profile between strong and weak self-assembling peptides. All these come together to suggest that the self-assembling behaviour of pepfactants is highly dependent on their structural flexibility.

Keywords::

• pepfactant
• self-assembly
• structural flexibility
• biomaterials

Acknowledgements

This work was supported by the Fundamental Research Funds for the Central Universities (Nos 2682013CX034 and SWJTU11ZT25).