Fig. 1: Computational design stages of the topological refactoring strategy.
From: A topological refactoring design strategy yields highly stable granulopoietic proteins
A X-ray structure of G-CSF (orange) bound to its cognate receptor (red) through its binding epitope (blue). B According to the topological refactoring strategy, the topology of the native G-CSF was rewired from around the fixed binding epitope. This was done by replacing the two long, bundle-spanning loops, by two short, de novo designed loops; reconstructing an up–up-down–down bundle into an up-down helical bundle. This resulted in much simpler contact maps, a lower contact-order, and a smaller protein (G-CSF residue numbering is based on PDB: 2D9Q). C The design models were further optimised in order to idealise the core packing (blue volume) and to hydrophilise residues distal from the binding epitope (orange crust).
