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(507c) Exploring Residue Roles in CATCH Peptide Co-Assembly

Hudalla, G. A., University of Florida
Seroski, D. T., University of Florida
Liu, R., University of Florida
Coassembling peptides can be assembled into biomaterials, such as scaffolds or hydrogels with tunable properties for use in biotechnological applications, such as chemical synthesis, biosensors, or tissue engineering. Peptide co-assembly refers to the spontaneous organization of two different molecules into a supramolecular architecture without any external guidance. The Hudalla group developed a highly-charged synthetic peptide that selectively assembles into ̫β-sheet nanofibers in the presence of a second charge-complementary peptide. These peptides are referred to as CATCH (Co-Assembly Tags based on CHarge complementarity) peptides.

Our research objective is to investigate how the amino acid sequence in CATCH peptides affects assembly dynamics, as well as the properties of the resulting hydrogel. Discontinuous Molecular Dynamics (DMD) simulations with the PRIME20 force field were used to examine the role of residue charge on co-assembly of binary CATCH(+) and CATCH(-) peptide mixtures. Here we focus on three CATCH peptide pairs with varied numbers of charged residues in each peptide: CATCH(2+/2-), CATCH(4+/4-), and CATCH(6+/6-). Atomistic simulations were used to investigate how the sidechain charge and length affect peptide co-assembly by swapping out glutamic acid residues for aspartic acid in CATCH(6+/6-). The use of simulations offer a unique insight into the co-assembly kinetics of CATCH peptides at the microsecond scale, inaccessible by conventional biophysical experimentation.

Our simulations elucidate the assembly pathway for CATCH peptides and suggest that increasing the number of charged amino acid residues within each peptide increases the rate of co-assembly. We have also shown that the side chain length of the negatively charged residue in CATCH influences the stability of the final CATCH β-sheet bilayer structure. From atomistic simulations, we found that structures built with a lysine rich peptide and an aspartic acid rich peptide (KQKFKFKFKQK and DQDFDFDFDQD) were more thermodynamically favorable than structures built with a lysine rich peptide and a glutamic acid rich peptide (KQKFKFKFKQK and EQEFEFEFEQE). Understanding the role of the amino acid side chain on hydrogel properties and assembly dynamics can help guide the development of biomaterials.