Analysis of energy stabilization inside the hydrophobic core of rubredoxin

The hydrophobic core of globular proteins is responsible for major stabilization of the protein tertiary structure. The prevailing amino-acid residues in the core are of aliphatic or aromatic character, and therefore, the core in a folded protein structure is mostly stabilized by noncovalent interactions of van der Waals origin between the amino-acid side chains. Herein, we present a theoretical analysis of the interaction energy between the amino acids of the hydrophobic core of the small globular protein rubredoxin (Rd) based on the symmetry-adapted perturbation theory (SAPT) method. The results show uniform proportions between the second-order dispersion and first-order electrostatic energy terms in favor of dispersion interaction, which plays a major role in the stabilization of this important structural element. To demonstrate the contrast between systems stabilized by different mechanisms, we perform a SAPT analysis of the typical hydrogen bonds involved in the formation of protein secondary structure elements in Rd, where dispersion still plays a non-negligible role but electrostatic energy is the major stabilizing factor.