Structure and Shape Effects of Molecular Glue on Supramolecular Tubulin Assemblies

The possibility to arrange biological molecules into ordered nanostructures is an important issue in nano- and biotechnology. Nature offers a wide range of molecular bricks (e.g., proteins, oligonucleotides, etc.) that spontaneously assemble into more complex hierarchical systems with unique functionalities. Such molecular building blocks can be also used for the construction of nanomaterials with peculiar properties (e.g., DNA origami). In some cases, molecular glues able to bind biomolecules and to induce their assembly can be used to control the final structure and properties in a convenient way. Here we provide molecular-level description of how molecular glues designed to stick to the surface of microtubules (MTs) can control and transform the alpha/beta-tubulin assembly upon temperature decreasing. By means of all-atom molecular dynamics (MD) simulations, we compared the adhesion to the MT surface of three molecular glues bearing the same guanidinium ion surface adhesive groups, but having different architecture, i.e., linear or dendritic backbone. Our evidence demonstrates that the adhesive properties of the different molecular glues are dependent on the shape they assume in solution. In particular, adhesion data from our MD simulations explain how globular- or linear-like molecular glues respectively stabilize MTs or transform them into a well-defined array of alpha/beta-tubulin rings at 15 degrees C, where MTs naturally depolymerize. The comprehension of the MT transformation mechanism provides a useful rationale for designing ad hoc molecular glues to obtain ordered protein nanostructures from different biological materials.