Polypeptoids have emerged as versatile sequence-programmable polymers that can be synthesized on gram scale with a growing variety of applications, including antifouling coatings, drug carriers, and selective ligands. With several force fields now available, simulations are well-posed to elucidate polypeptoid configurational landscapes, interactions, and structure-property relations, but are currently severely challenged by slow intramolecular conformational dynamics that preclude modeling long chains (more than five monomers) and multi-molecular polypeptoid assemblies.  As the same time, these sampling challenges have limited the ability to test and validate existing forcefields’ ability to reproduce actual conformational distributions for a diverse array of sequences.  Here, we develop advanced molecular dynamics simulation techniques to surmount these challenges and to investigate the behavior of a variety of model polypeptoid sequences of systematically varied hydrophobicity.  We overcome long-timescale polypeptoid dynamics through a novel expanded ensemble approach that fully samples over the slow conformational motions, making simulations of long sequences tractable and enabling detailed comparisons with experimental results on a variety of systems. Specifically, to critically assess the accuracy of the force fields and overall modeling strategy, our simulations are benchmarked against Double Electron-Electron Resonance (DEER) spectroscopic measurements that quantify the end-to-end distance distributions of each polypeptoid sequence.  We thus first evaluate the accuracy of current polypeptoid force fields by comparing simulation end-to-end distributions for length- and hydrophobicity-varied sequences with those measured from DEER experiments. We then use simulations to develop scaling laws and qualitative trends for the polypeptoid conformational distribution and thermodynamics in terms of the number, sequence, and chemistry of hydrophobic monomers.

Quantifying polypeptoid conformational landscapes through advanced sampling molecular simulation and spectroscopy

Macromolecular Chemistry: The Second Century

[Author Benefits](https://scimeetings.acs.org/?utm_source=pubs_content_marketing&utm_medium=website&utm_campaign=0320_MCF_NPI_Launch_Spring_Homepage&ref=pubs_content_marketing)

[How to use SciMeetings](https://storage.googleapis.com/dl.morressier.com/acs/SciMeetings-ACSSpring2020-HowToGuide_M3020-Final.pdf)

[Frequently Asked Questions](https://storage.googleapis.com/dl.morressier.com/acs/SciMtng_ACSNMSp2020_FAQ_M3120_Final.pdf)

ACS Spring 2020 National Meeting & Expo

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