A protein self-assembly model guided by electrostatic and hydrophobic dipole moments

Abstract

Protein self-assembling is studied under the light of the Biological Membrane model. To this purpose we define a simplified formulation of hydrophobic interaction energy in analogy with electrostatic energy stored in an electric dipole. Self-assembly is considered to be the result of the balanced influence of electrostatic and hydrophobic interactions, limited by steric hindrance as a consequence of the relative proximity of their components. Our analysis predicts the type of interaction that drives an assembly. We study the growth of both electrostatic and hydrophobic energies stored by a protein system as it self-assembles. Each type of assembly is studied by using two examples, PDBid 2OM3 (hydrophobic) and PDBid 3ZEE (electrostatic). Other systems are presented to show the application of our procedure. We also study the relative orientation of the monomers constituting the first dimer of a protein assembly to check whether their relative position provides the optimal interaction energy (energy minimum). It is shown that the inherent orientation of the dimers corresponds to the optimum energy (energy minimum) of assembly compatible with steric limitations. These results confirm and refine our Biological Membrane model of protein self-assembly valid for all open and closed systems.

How hydrophobicity shapes the architecture of protein assemblies

“…The final fibres are formed by joining two of these stacks so that their hydrophobic vectors oppose each other, as would happen with a biological membrane (Fig. 1 ) [ 18 , 21 , 28 ]. A simulation of rotation (Fig.…”

Use of vector formalism in the analysis of hydrophobic and electric driving forces in biological assemblies

“…), are addressed in 3D. Hence, H and D directly indicate the direction and magnitude of the hydrophobic and electrical anisotropies (Mozo-Villarías et al, 2014Mozo-Villarías and Querol, 2019). This review shows examples of DNA and protein behaviour as well as protein self-assembly and interactions with DNA.…”

“…This method focuses on two concepts: the hydrophobic moment and the hydrophobic energy of interaction between molecules or complexes as described in the following sections. The interaction of these hydrophobic moments is modelled by using the so-called ‘biological membrane’ model (BM model, Mozo-Villarías et al ., 2014, 2016, 2017; Mozo-Villarías and Querol, 2019), according to which the hydrophobic moments of macromolecules tend to align like phospholipids in the double layer of a membrane. The hydrophobic tails of the phospholipids tend to hide from the aqueous medium while the hydrophilic heads are exposed to the aqueous medium, as is well known (Fig.…”

“…Analogously, considering the individual hydrophobicities of each amino acid as hydrophobic ‘charges’, the interaction energy between two hydrophobic dipoles H 1 and H 2 is postulated (Mozo-Villarías and Querol, 2019) as:where the constant k is taken as 1.…”

“…Mozo-Villarías et al . (2014, 2017, 2019) described a number of amyloid complexes of various types, finding interactions between the H and D vectors following the effect of the BM model.…”