There is the fact that proteins are constrained to function as part of organisms that are capable of self-replication. This constraint means that proteins (mostly) are not very stable wrt oxidisation and UV degradation, and only work properly in aqueous solution.<p>It&#x27;s anyone&#x27;s guess how significant these constraints will be from the viewpoint of developing artificial protein machines (maybe rapid (bio)degradation is a good thing!), but there&#x27;s definitely large swathes of chemical design space outside of arbitrary chains of known amino acids, and we might be able to discover entire classes of molecular machines that don&#x27;t have the drawbacks of bioinspired proteins.