Interaction of Coiled Coil Peptides

• Dylan Stare, Chemical Engineering, University of Delaware

• Eric Furst, Chemical and Biomolecular Engineering, University of Delaware

Bundlemers are a class of computationally designed peptide sequences which spontaneously self-assemble in aqueous solutions into tetra-helical coiled coil “nanoparticles”. This self-assembly is governed by the positioning of hydrophobic residues within the peptide chain. Provided they remain unperturbed, the remaining amino acids can be readily substituted with any other hydrophilic residue. Different bundlemer sequences have different solution phase behavior; some stay well dispersed in solution while others form soluble aggregates. A bundlemer with higher surface charge will tend to remain dispersed while one with lower surface charge may form soluble aggregates. Previous work on protein docking computation neglected electrostatics in favor of hard-sphere attraction models. However, due to their high surface charge density, the assumption of negligible electrostatics should not hold for bundlemer peptides under reasonable ionic strength conditions (30-100 mM). Combining pair-wise coulombic potentials with non-electrostatic models produces an energy potential similar to DLVO theory– a model used to characterize the aggregation of colloidal systems. The energy potential of the interaction between two copies of the peptide may be measured through an atomwise approach. The interaction space for this calculation is defined through a combination of spherical coordinates (⍴, φ, θ) and rotational Tait-Bryan angles (α, β, γ) with the rotation order ZYX chosen arbitrarily to ensure consistent results across trials. The focus of this work is to compare results for +24E and +24Q bundlemer sequences– peptide chains with the same net charge but different residue combinations, which result in unique placement of charge patches. The +24Q sequence generally features greater negative energy potentials in both the non-electrostatic and electrostatic regimes under large sample sizes (n = 10,000), indicating colloidal aggregation would be more likely observed in solution when the ionic strength is sufficiently high enough to screen out electrostatic interactions compared to +24E at the same conditions.