Protein - Noncovalent interactions

Introduction

Noncovalent interactions are very common in macromolecules (including proteins), due to the relative weakness of these interactions.

Indeed, whereas covalent bonds require an energy input of 65 to 175 kcal/mol to be broken, the energy content of a noncovalent bond is only up to a few kcal/mol. As explained above, the weakness of these interactions allows proteins to change conformation and bind ligands, two properties that are highly important for their function. Although they are weak, the high number of noncovalent interactions still allows them to stabilize three-dimensional protein structures. The nature and strength of noncovalent interactions in a protein are affected by the chemical nature of the protein’s environment. It is therefore customary when discussing protein structure to take into consideration not only the protein and any ligand it may bind (both are referred to as the ‘solute’), but also the molecules constituting their environment (referred to as the ‘solvent’).

There are two main types of noncovalent interactions:

1. Electrostatic interactions – These are interactions that occur between electrically charged atoms, and include both attractive and repulsive forces. The charges may be full or partial*1, and partial charges may be fixed or induced (see details below). One class of electrostatic interactions, van der Waals interactions, occur between induced partial charges. This type of interaction has several unique features (e.g., it occurs between any pair of atoms that are close enough to each other) and is therefore described separately from other electrostatic interactions.

2. Nonpolar interactions – These attractive interactions, resulting from the hydrophobic effect, are most noticeable between atoms or chemical groups that are devoid of charge.

Electrostatic interactions

Two atoms that are electrically charged interact electrostatically with each other.

The nature of these interactions depends on the signs of the charges; charges of the same sign repel each other, and charges of opposite sign attract each other.

Each of the interacting charges generates an electric field, which surrounds it. The interaction between the two charges results from the way the electric field emanating from one charge affects the other charge. Since both full and partial charges may be involved, there are various types of electrostatic interactions between atoms, including charge-charge, charge-dipole, and dipole-dipole, where the latter two may involve fixed or induced dipoles.

In proteins, the most common interactions (except for van der Waals interactions, which will be discussed separately) are: