The folding of most proteins from a primary (linear) sequence of amino acids to a three-dimensional structure is governed by many factors, including non-covalent interactions. The first ~5 milliseconds of folding are primarily dependent on van der Waals forces, whereby the protein folds so as to orient nonpolar amino acids in the interior of the globular protein, while more polar amino acid residues are exposed to aqueous solvent. This phase is known as the hydrophobic collapse, when nonpolar non-covalent interactions exclude water from the interior of the developing 3D protein structure.