Programming co-assembled peptide nanofiber morphology via anionic amino acid type: Insights from molecular dynamics simulations

PLoS Comput Biol. 2023 Dec 4;19(12):e1011685. doi: 10.1371/journal.pcbi.1011685. eCollection 2023 Dec.

Abstract

Co-assembling peptides can be crafted into supramolecular biomaterials for use in biotechnological applications, such as cell culture scaffolds, drug delivery, biosensors, and tissue engineering. Peptide co-assembly refers to the spontaneous organization of two different peptides into a supramolecular architecture. Here we use molecular dynamics simulations to quantify the effect of anionic amino acid type on co-assembly dynamics and nanofiber structure in binary CATCH(+/-) peptide systems. CATCH peptide sequences follow a general pattern: CQCFCFCFCQC, where all C's are either a positively charged or a negatively charged amino acid. Specifically, we investigate the effect of substituting aspartic acid residues for the glutamic acid residues in the established CATCH(6E-) molecule, while keeping CATCH(6K+) unchanged. Our results show that structures consisting of CATCH(6K+) and CATCH(6D-) form flatter β-sheets, have stronger interactions between charged residues on opposing β-sheet faces, and have slower co-assembly kinetics than structures consisting of CATCH(6K+) and CATCH(6E-). Knowledge of the effect of sidechain type on assembly dynamics and fibrillar structure can help guide the development of advanced biomaterials and grant insight into sequence-to-structure relationships.

MeSH terms

  • Amino Acids
  • Biocompatible Materials
  • Molecular Dynamics Simulation
  • Nanofibers* / chemistry
  • Peptides / chemistry

Substances

  • Amino Acids
  • Peptides
  • Biocompatible Materials