The hydrophobic interaction (HI) is a complex thermodynamic force that plays a critical role in peptide folding and self-assembly processes.  Here, we discuss two approaches to modeling HIs informed by simulation studies of model systems. First, we discuss a combined experimental-simulation approach to characterize HIs and their scaling behavior using a model hydrophilic peptide scaffold onto which hydrophobic leucine mutations can be systematically introduced.  Single-molecule AFM experiments show that the free energy to remove these peptides from a hydrophobic surface scales linearly with the number of leucine residues, at 3.4 kT/leucine, and complementary atomistic simulations are in close agreement.  Moreover, the simulations reveal that the three-body water angle distribution, which characterizes both tetrahedral and non-tetrahedral water structure, provides a molecular structural signature of the strength of the HI in each case. Second, we show that HIs can be modeled at a very coarse-grained level using a novel simulation approach inspired by multibody treatments of metallic interactions.  Namely, this strategy uses systematic bottom-up coarse graining techniques to develop accurate “local water density” potentials that provide a realistic and transferable description of HI driving forces.

Hydrophobic interactions in peptide folding, association, and assembly

253rd National Meeting (2017)

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