Mussels can strongly adhere to hydrophilic minerals in sea habitats by secreting adhesive proteins. The adhesion ability of these proteins is often attributed to the presence of Dopa derived from posttranslational modification of Tyr, whereas the contribution of structural feature is overlooked. It remains largely unknown how adhesive proteins overcome the surface-bound water layer to establish underwater adhesion. Here, we use molecular dynamics simulations to probe the conformations of adhesive protein Pvfp-5β and its salt-tolerant underwater adhesion on superhydrophilic mica. Dopa and positively charged basic residues form pairs, in this intrinsically disordered protein, and these residue pairs can lead to firm surface binding. Our simulations further suggest that the unmodified Tyr shows similar functions on surface adhesion by forming pairing structure with a positively charged residue. We confirm the presence of these residue pairs and verify the strong binding ability of unmodified proteins using nuclear magnetic resonance spectroscopy and lap shear tests.

Recent experiments suggested that ATP can effectively stabilize protein structure and inhibit protein aggregation when its concentration is less than 10 mM, which is significantly lower than cosolvent concentrations required in conventional mechanisms. The ultrahigh efficiency of ATP suggests a unique mechanism that is fundamentally different from previous models of cosolvents. In this work, we used molecular dynamics simulation and experiments to study the interactions of ATPs with three proteins: lysozyme, ubiquitin, and malate dehydrogenase. ATP tends to bind to the surface regions with high flexibility and high degree of hydration. These regions are also vulnerable to thermal perturbations. The bound ATPs further assemble into ATP clusters mediated by Mg 2+ and Na + ions. More interestingly, in Mg 2+ -free ATP solution, Na + at higher concentration (150 mM under physiological conditions) can similarly mediate the formation of the ATP cluster on protein. The ATP cluster can effectively reduce the fluctuations of the vulnerable region and thus stabilize the protein against thermal perturbations. Both ATP binding and the considerable improvement of thermal stability of ATP-bound protein were verified by experiments.

Amyloid fibrils were first investigated due to their close association with neurodegenerative diseases, including Alzheimer's, Parkinson's, and Huntington's diseases, [2] wherein soluble peptides/ proteins self-assemble into highly ordered fibrillar structures. [3] Interestingly, subsequent studies have found that amyloid fibrils also play important functional roles in various organisms, including bacteria, [4] insects, [5] and mammals. [6] Moreover, amyloid peptides can self-assemble into highly ordered nanostructures with favorable properties, such as high thermal stability and stiffness as well as biocompatibility. [7] These peptide nanostructures show great promise in tissue engineering, [8] retroviral gene transfer, [9] nanowires, [10] light harvesting, [11] and catalysis. [12] Therefore, new insights into the self-assembly of amyloid-like peptides not only help reveal the pathogenesis of various neurodegenerative diseases but also facilitate the de novo design and fabrication of biomoleculebased nanodevices. Previous studies have suggested that the lipid membrane surface influences the assembly kinetics and morphology of amyloid peptide aggregates. [13] However, cellular membranes and associated physiological conditions are generally too heterogeneous and complex for a clean study of surface-assisted Insight into the surface-assisted self-assembly of amyloid-like peptides is essential to the design and fabrication of novel functional nanomaterials as well as to uncovering the pathogenesis of various neurodegenerative diseases. Despite extensive research, how to control the self-assembly of amyloid-like peptides effectively remains challenging. Here, through a combined experimental and theoretical approach, it is demonstrated that cations could modulate the mica/water interface and further induce the self-assembly of the negatively charged amyloid-like peptide Ac-VGGAVVAGV-COO − (Ac-GAV-9) into multilayered nanofilaments with a surprising all-upright parallel β-sheet conformation. In particular, highly ordered double-layered nanofilaments are observed on the negatively charged mica surfaces in the presence of 0.5-1.5 m KCl. The molecular dynamics simulations further reveal that the double-layered nanofilaments have intriguing parallel β-sheet structures with the C-termini of the first parallel monolayer pointing to the mica surface and the C-termini of the second parallel monolayer pointing to the solvent. Moreover, the stability of the nanofilaments could be modulated by peptide and ion concentrations. Further studies show that the growth of double-layered fibrils at the mica/water interface is a common phenomenon for Ac-GAV-9 in the presence of a variety of salt types.