Fig. 2: De novo design of l-protein-targeting d-proteins using an integrated computational and experimental method.
From: Accurate de novo design of heterochiral protein–protein interactions
a Key steps in the de novo design method. Pre-generated l-rotamers that interact with the selected surface region of the d-protein target are shown in lines (left panel). Mini-protein scaffolds docked on the d-protein target are shown in cartoon, with the target-interacting side chains highlighted in spheres (middle panel). Positions on the mini-protein at the interface are further designed for optimized binding (shown in spheres, right panel). b High-throughput experimental validation, integrating yeast display (right), directed evolution (middle) and binding affinity measurement (left). The loop arrow indicates that it is possible to obtain high-affinity binders directly from a designer library, without the need for any affinity maturation process. All structural images were generated by using PyMOL.63
