The biomimetic oligomer meta-poly(phenylene ethynylene) (mPPE) is modeled to gain an understanding of the functionality of many transmembrane proteins, which are similar in structure, but often too large and computationally expensive to model. Most of the prior studies feature mPPEs that are known experimentally to be water-insoluble, which places limitations on the applicability of these studies’ findings to biologically relevant problems. The objective of this study was to parameterize models for experimentally-known mPPE foldamers, propose and test a collection of metrics for water-solubility of mPPE foldamers, and to study diffusion of solvent and ions through the cavity of mPPE helices. Models of the mPPE were constructed based on the intramolecular parameters in the CHARMM General Force Field (CGenFF) and CHARMM35 force field. Appropriate partial charges for the monomers were computed using the MP2/6-31G(d) level of theory and the Merz-Kollman scheme. Production runs of simulations were run in the dynamics package NAMD2. Using the computational models developed, metrics of solubility were elucidated from simulations of foldamers known to be experimentally water-soluble (hexaethylene glycol and ethylammonium side chains) and water-insoluble (triethylene glycol, methyl ester, and ethylamine side chains). The metrics developed include number of monomers per turn of helix, numbers of solvent molecules within helix, and solvent accessible surface area. The kinetics of the diffusion of ions through the center of the helix were also examined. The solvophobic interactions involved in the diffusion process were studied, as well as the effects of helix length and adding an endohelical side chain. Endohelical functional groups were found to have a significant impact on the diffusion rates through the helix. The use of polar or charged endohelical functional groups could functionalize the foldamers as chemoselective molecular sieves. Furthermore, synthetic proteins could possibly forge a future approach towards facilitated transport through membrane barriers.

Effects of exohelical functionalization on structure of water-soluble meta-poly(phenylene ethynylene) foldamers

251st National Meeting (2016)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.