Tuning interactions between hybrid physical-covalent rigid rods made of computationally designed coiled coils by peptide sequence manipulation

Application of computational design to biomolecular sequence, structure and function prediction provides vast opportunity in artificial biomaterial construction and assembly. Non-natural coiled coils, oligomers of α-helical peptides, can be designed to assemble in solution by computational sequence discovery and manipulation via strategic placement of amino-acids exposed to the solvent. Utilizing a hybrid assembly pathway, computationally designed homotetramer coiled coil bundles are linked in an end-to-end fashion resulting in rigid rods of bundles or “bundlemers”. Transmission Electron Microscopy (TEM) and Small-Angle Neutron Scattering (SANS) confirm that the rods have a 2 nm cross-section commensurate with that of a single bundle. SANS is also used to study inter-rod interactions for peptides that carry increasing net negative charge. Differences in local repulsive interactions between rods is observed due to changes in rod charge density, which is responsive to pH and ionic strength of the solution. Larger percolated clusters of rods which form due to local patchiness of interaction sites is also confirmed. This control of solution structure with fine control of the charged state, length, dispersity and concentration of bundlemer rods will be discussed.