Intramolecular structure and dynamics in computationally designed peptide-based polymers displaying tunable chain stiffness

Bioorthogonal Polymerization of Coiled-Coil Peptides

“…21), our analyses revealed that poly(DE4)n (reduced χ 2 = 1.12) had a radius of 1.3 nm and an average Kuhn length of 6.3 nm with a standard deviation of 1.3 nm. This Kuhn length is slightly smaller than the previously reported 7.1 ± 1 nm for semiflexible bundlemer chains 39 linked with a 4-arm PEG linker but is still indicative of a single bundlemer persistance length.…”

“…License: CC BY-NC-ND 4.0 reasonably well (reduced chi-squared, χ 2 = 1.43) to a cylinder model with a length of 6.7 nm and a radius of 1.2 nm. This radius is consistant with the values for previously published bundlemers, while the length is consistant with a typical bundlemer (l = 3.6 -4.5 nm) 12,18,[36][37][38][39] plus extended PEG linkers at each N-termini. Treating poly(DE4)n as a series of rigid bundlemer segments connected by flexible PEG linkers, we fitted it to a flexible cylinder model in SASview as has been previously done for semiflexible bundlemer rods 12,39 .…”

“…This radius is consistant with the values for previously published bundlemers, while the length is consistant with a typical bundlemer (l = 3.6 -4.5 nm) 12,18,[36][37][38][39] plus extended PEG linkers at each N-termini. Treating poly(DE4)n as a series of rigid bundlemer segments connected by flexible PEG linkers, we fitted it to a flexible cylinder model in SASview as has been previously done for semiflexible bundlemer rods 12,39 . Additionally, given the relatively long and flexible nature of the PEG linker, with a total of 7 ethylene oxide repeats between adjacent bundlers, it is unlikely for the polymer to have a singular fixed Kuhn length, but instead a range of Kuhn lengths dependent on whether PEG is extended or collapsed.…”

Computational Design of Homotetrameric Peptide Bundle Variants Spanning a Wide Range of Charge States

“…In previous studies, related 29-residue D 2 symmetric homotetrameric bundles were covalently linked via functionalization of their N-termini to yield rigid polymers. − Charged bundles designed herein can be similarly polymerized. The polymer comprises two types of bundle monomers (bundlemers − ), each having different functionalization at the N-terminus of the peptide: (a) a bundle with maleimide (Mal) attached via the amino terminus and (b) a 30-residue bundle with an additional Cys residue at the N-terminus (Figure a). Given the antiparallel D 2 symmetry, each end of the corresponding bundle monomer displays (a) two maleimide groups or (b) two thiol groups.…”

“…There have been efforts to engineer large-scale variation of charge via substitution of ionizable residues both to implement specific functionalities and to investigate the electrostatic effects of charges on protein association. , Recent efforts have focused on engineering supercharged variants of proteins, − tuning the solubility of membrane proteins by modifying surface charges, − creating uncharged or highly charge-depleted proteins, , and peptides containing only one type of charge . Complementary electrostatic charge has also been used to develop large, nanostructured assemblies from engineered protein building blocks. ,, Linked chains of charged proteins have provided vehicles for studying polyelectrolyte properties with precisely engineered polymers. − Engineering a wide variation of charge states can be subtle; however, substitutions can often yield unstructured or aggregation-prone sequences. As a result, methods that can address large variation in sequence are usually employed, such as directed evolution , and computational protein design. − ,, …”