The folding of proteins from a primary (linear) sequence of amino acids to a three-dimensional structure is directed by all types of  non-covalent interactions, including the hydrophobic forces and formation of intramolecular hydrogen bonds. Three-dimensional structures of proteins, including the secondary and tertiary structures, are stabilized by formation of hydrogen bonds. Through a series of small conformational changes, spatial orientations are modified so as to arrive at the most energetically minimized orientation achievable. The folding of proteins is often facilitated by enzymes known as molecular chaperones. Sterics, bond strain, and angle strain also play major roles in the folding of a protein from its primary sequence to its tertiary structure.
Single tertiary protein structures can also assemble to form protein complexes composed of multiple independently folded subunits. As a whole, this is called a protein's quaternary structure. The quaternary structure is generated by the formation of relatively strong non-covalent interactions, such as hydrogen bonds, between different subunits to generate a functional polymeric enzyme. Some proteins also utilize non-covalent interactions to bind cofactors in the active site during catalysis, however a cofactor can also be covalently attached to an enzyme. Cofactors can be either organic or inorganic molecules which assist in the catalytic mechanism of the active enzyme. The strength with which a cofactor is bound to an enzyme may vary greatly; non-covalently bound cofactors are typically anchored by hydrogen bonds or electrostatic interactions.