How hydrophobicity shapes the architecture of protein assemblies.

The interactions that give rise to protein self-assembly are basically electrical and hydrophobic in origin. The electrical interactions are approached in this study as the interaction between electrostatic dipoles originated by the asymmetric distribution of their charged amino acids. However, hydrophobicity is not easily derivable from basic physicochemical principles. Its treatment is carried out here considering a hydrophobic force field originated by "hydrophobic charges". These charges are indices obtained experimentally from the free energies of transferring amino acids from polar to hydrophobic media. Hydrophobic dipole moments are used here in a manner analogous to electric dipole moments, and an empirical expression of interaction energy between hydrophobic dipoles is derived. This methodology is used with two examples of self-assembly systems of different complexity. It was found that the hydrophobic dipole moments of proteins tend to interact in such a way that they align parallel to each other in a completely analogous way to how phospholipids are oriented in biological membranes to form the well-known double layer. In this biological membrane model (BM model), proteins tend to interact in a similar way, although in this case this alignment is modulated by the tendency of the corresponding electrostatic dipoles to counter-align. Helical conformation of influenza virus PDBid: 6Z5L. Two monomers are shown in cyan and green. The corresponding dipole moment vectors are shown in red (electric dipoles) and blue (hydrophobic dipoles). From the inset figure, it can be seen that the growth of the helix is due to electrical attraction of the monomers, overcoming a hydrophobic repulsion (see text).