Biomimetic polymers (BMPs) are useful for materials science and bioenergy applications like CO2 separation because of a diverse availability of monomers, high thermostability, and resistance to biodegradation. We have been developing a multi-scale simulation framework to facilitate experimental design and development of BMP systems, with the goal of forming ordered structures and pore networks. These simulations also provide insights about the key forces governing folding and assembly in such systems, which are currently poorly understood.
For example, experiments show that amphiphilic peptoid BMPs form fibers in solution and/or micron-scale bilayers on a mica surface. Peptoids are challenging to simulate because the amide bonds between residues can isomerize between cis and trans and the peptoid amide cannot form backbone-backbone hydrogen bonds. In addition, replica-exchange molecular dynamics (REMD) atomistic simulations of dimers of these 12-residue peptoids do not reproduce the experimental structural forms. Thus, we are developing a MARTINI-based coarse-grained (CG) force field for the peptoid backbone to model cooperative assembly at larger length scales. For bonded terms, atomistic simulations show that the backbone Ni-Nj distance is consistently 0.37 nm, while the Ni-Nj-Nk pseudo-angle clearly distinguishes the cis and trans states of the amide bond between residues i and j. For non-bonded parameters, we create a new particle type from the MARTINI P3 type that reflects the unusual hydrogen bonding properties of the peptoid amide. CG simulations of all-trans sarcosine 12-mer recover the bonded potentials seen in a corresponding atomistic simulation, and they also qualitatively reproduces the atomistic radius of gyration (Rg) distribution.
In a parallel example, we are structurally modeling different sequences of a new polymer architecture, in which variable-length non-amide linkers connect core elements bearing sidechains, to inform experimental designs. The cores and linkers are parameterized using the generalized amber force field, and 500-ns REMD simulations are used to explore the conformational space of short polymers. K-means clustering is used to identify favored structures. Simulations of hexamers suggest several favored motifs with different backbone/backbone hydrogen bonding and π stacking configurations. The simulations also suggest that imine sidechains increase helical propensity, chiral linkers increase conformational order, and longer linkers promote more globular structures. We are currently performing experiments to test these simulation-based hypotheses. In simulations of 12-mers, more globular and elaborate tertiary structures form that are reminiscent of proteins. This suggests significant promise of the novel polymer architecture for applications where intramolecular conformational and structural order are functionally important.