Design of Diverse Asymmetric Pockets in De Novo Homo-oligomeric Proteins.

ABSTRACT: A challenge for design of protein-small-molecule recognition is that incorporation of cavities with size, shape, and composition suitable for specific recognition can considerably destabilize protein monomers. This challenge can be overcome through binding pockets formed at homo-oligomeric interfaces between folded monomers. Interfaces surrounding the central homo-oligomer symmetry axes necessarily have the same symmetry and so may not be well suited to binding asymmetric molecules. To enable general recognition of arbitrary asymmetric substrates and small molecules, we developed an approach to designing asymmetric interfaces at off-axis sites on homo-oligomers, analogous to those found in native homo-oligomeric proteins such as glutamine synthetase. We symmetrically dock curved helical re

SUBMITTER: Gerben SR 

PROVIDER: S-EPMC9850923 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature