There is a growing interest in biomaterials with spatially-defined and reconfigurable mechanical properties. For example, a gradient of elastic properties is essential in applications where soft materials join hard substrates. Materials with tunable mechanical properties can be engineered using proteins as structural components, and many of the functional properties of biological materials have been attributed to the presence of metal centers. One such biological structure that takes advantage of non-mineralized, proteinaceous material containing metal centers is the Nereis virens worm jaw which is used for grasping, piercing, and tearing. The hardness and stiffness of the Nereis jaw are comparable to mineralized biomaterials, such as dentin. The jaw protein, Nvjp-1 is primarily composed of glycine, histidine, acidic residues, and tyrosine. In this study, metal coordination of Nvjp-1 in a salt solution in the presence of Zn2+ is investigated by all-atom molecular dynamics simulations that employ a polarizable force field. The protonation state of the protein determines which types of residues capture zinc ions from the solution. At pH = 5 in ZnCl2, polar residues, such as tyrosine, predominantly interact with Zn2+, forming coordination bonds with at most two residues interacting with a single zinc ion. At this pH, negatively charged residues form salt bridges with protonated histidines and are effectively blocked from interacting with zinc ions. Changing the protonation state of the Nvjp-1 to reflect a pH of 8, and removing all unbound zinc ions, leads to the formation of new coordinate bonding with histidine and acidic residues where up to four residues interact with a single zinc ion. An accompanying reduction in the radius of gyration is taken as evidence of protein condensation and sclerotization. This study also looks at the role of the anion partner of zinc in terms of zinc coordination and the effect on the Nvjp-1 radius of gyration. Together, these simulations indicate that pH and anions strongly influence metal loading and crosslinking of the Nvjp-1 protein through modulation of amino acid side chain interactions. Additionally, these studies show how a pH-driven, metal-binding hierarchy can be functionally important in regulating the mechanical properties of an intrinsically disordered structural protein.

Molecular dynamics investigation of metal coordination in a structural jaw protein from a marine sandworm

ACS Fall 2021

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