<i>De novo</i> designed 3-helix bundle peptides and proteins with controlled topology and stability.

ABSTRACT: Computational protein design is advancing rapidly. However, approaches and methods are needed to increase success rates and to elaborate designs. Here we describe the combination of rational and computational design to deliver three-helix bundle (3HB) peptide assemblies and single-chain proteins with control over topology and thermal stability. First, we garner sequence-to-structure relationships from antiparallel 3HBs in the Protein Data Bank. This gives core-packing rules, including layers of hydrogen-bonded polar residues, which are combined with surface-charge patterning to design complementary sequences for acidic (A), basic (B), and neutral (N) helices. By altering the design of the N helix, two sets of synthetic peptides are generated for clockwise and anticlockwise arrangements of

SUBMITTER: Leng X 

PROVIDER: S-EPMC12441935 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature