Halogen bonding interactions between halogenated ligands and proteins were examined using the crystal structures deposited to date in the PDB. The data was analyzed as a function of halogen bonding to main chain Lewis bases, viz. oxygen of backbone carbonyl and backbone amide nitrogen. This analysis also examined halogen bonding to side-chain Lewis bases (O, N, and S) and to the electron-rich aromatic amino acids. All interactions were restricted to van der Waals radii with respective atoms. The data reveals that while fluorine and chlorine have strong tendencies favoring interactions with the backbone Lewis bases at glycine, the trend is not restricted to the achiral amino acid backbone for larger halogens. Halogen side-chain interactions are not restricted to amino acids containing O, N, and S as Lewis bases. Electron-rich aromatic amino acids host a high frequency of halogen bonds as does Leu. A closer examination of the latter hydrophobic side chain reveals that the "propensity of interactions" of halogen ligands at this oily residue is an outcome of strong classical halogen bonds with Lewis bases in the vicinity. Finally, an examination of Θ1 (C-X···O and C-X···N) and Θ2 (X···O-Z and X···N-Z) angles reveals that very few ligands adopt classical halogen bonding angles, suggesting that steric and other factors may influence these angles. The data is discussed in the context of ligand design for pharmaceutical applications.

We describe here the construction of a three-dimensional, porous, crystalline framework formed by spherical protein nodes that assemble into a prescribed lattice arrangement through metal-organic linker-directed interactions. The octahedral iron storage enzyme, ferritin, was engineered in its C3 symmetric pores with tripodal Zn coordination sites. Dynamic light scattering and crystallographic studies established that this Zn-ferritin construct could robustly self-assemble into the desired bcc-type crystals upon coordination of a ditopic linker bearing hydroxamic acid functional groups. This system represents the first example of a ternary protein-metal-organic crystalline framework whose formation is fully dependent on each of its three components.

The formation of condensed matter typically involves a trade-off between structural order and flexibility. As the extent and directionality of interactions between atomic or molecular components increase, materials generally become more ordered but less compliant, and vice versa. Nevertheless, high levels of structural order and flexibility are not necessarily mutually exclusive; there are many biological (such as microtubules, flagella , viruses) and synthetic assemblies (for example, dynamic molecular crystals and frameworks) that can undergo considerable structural transformations without losing their crystalline order and that have remarkable mechanical properties that are useful in diverse applications, such as selective sorption , separation , sensing and mechanoactuation . However, the extent of structural changes and the elasticity of such flexible crystals are constrained by the necessity to maintain a continuous network of bonding interactions between the constituents of the lattice. Consequently, even the most dynamic porous materials tend to be brittle and isolated as microcrystalline powders , whereas flexible organic or inorganic molecular crystals cannot expand without fracturing. Owing to their rigidity, crystalline materials rarely display self-healing behaviour . Here we report that macromolecular ferritin crystals with integrated hydrogel polymers can isotropically expand to 180 per cent of their original dimensions and more than 500 per cent of their original volume while retaining periodic order and faceted Wulff morphologies. Even after the separation of neighbouring ferritin molecules by 50 ångströms upon lattice expansion, specific molecular contacts between them can be reformed upon lattice contraction, resulting in the recovery of atomic-level periodicity and the highest-resolution ferritin structure reported so far. Dynamic bonding interactions between the hydrogel network and the ferritin molecules endow the crystals with the ability to resist fragmentation and self-heal efficiently, whereas the chemical tailorability of the ferritin molecules enables the creation of chemically and mechanically differentiated domains within single crystals.

Previously, we adopted the construction principles of metal-organic frameworks (MOFs) to design a 3D crystalline protein lattice in which pseudospherical ferritin nodes decorated on their C symmetric vertices with Zn coordination sites were connected via a ditopic benzene-dihydroxamate linker. In this work, we have systematically varied both the metal ions presented at the vertices of the ferritin nodes (Zn(II), Ni(II), and Co(II)) and the synthetic dihydroxamate linkers, which yielded an expanded library of 15 ferritin-MOFs with the expected body-centered (cubic or tetragonal) lattice arrangements. Crystallographic and small-angle X-ray scattering (SAXS) analyses indicate that lattice symmetries and dimensions of ferritin-MOFs can be dictated by both the metal and linker components. SAXS measurements on bulk crystalline samples reveal that some ferritin-MOFs can adopt multiple lattice conformations, suggesting dynamic behavior. This work establishes that the self-assembly of ferritin-MOFs is highly robust and that the synthetic modularity that underlies the structural diversity of conventional MOFs can also be applied to the self-assembly of protein-based crystalline materials.

A large fraction of proteins naturally exist as symmetrical homooligomers or homopolymers 1. The emergent structural and functional properties of such protein assemblies have inspired extensive efforts in biomolecular design 2-5. As synthesized by ribosomes, proteins are inherently asymmetric. Thus, they must acquire multiple surface patches that selectively associate to generate different symmetry elements needed to form higher-order architectures 1,6-a daunting task for protein design. Here we introduce an inorganic chemical approach to address this outstanding problem, whereby multiple modes of protein-protein interactions and symmetry are simultaneously achieved by selective, "one-pot" coordination of soft and hard metal ions. We show that a monomeric protein (protomer) appropriately modified with biologically inspired hydroxamate groups and Zn-binding motifs assembles through concurrent Fe 3+ and Zn 2+ coordination into discrete dodecameric and hexameric cages. Closely resembling natural polyhedral protein architectures 7,8 and unique among designed systems 9-13 , our artificial cages possess tightly packed shells devoid of large apertures, yet they can assemble and disassemble in response to diverse stimuli owing to their heterobimetallic construction on minimal interproteinbonding footprints. With stoichiometries ranging from [2 Fe:9 Zn:6 protomer] to [8 Fe:21 Zn:12 protomer], these protein cages represent some of the compositionally most complex protein assemblies-or inorganic coordination complexes-obtained by design. Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: