Within an integral membrane protein, a transmembrane helix is a segment that is alpha-helical in structure, roughly 20 amino acids in length and (though it may be presumed to lie within the protein, out of contact with the surrounding lipid bilayer) is said to "span" the membrane. Because membrane proteins are difficult to crystallize for structural determination by X-ray diffraction, protein segments only rarely are actually confirmed to be transmembrane helices, but are typically predicted on the basis of hydrophobicity. Because the interior of the bilayer and the interiors of most proteins of known structure are hydrophobic, it is presumed to be a requirement of the amino acids that span a membrane that they be hydrophobic as well. An alpha helix of about 20 amino acids long is the minimum required to span the width of the hydrophobic core of a lipid bilayer, although the exact thickness depends on the species of lipids. Using hydrophobicity analysis to predict transmembrane helices enables a prediction in turn of the "transmembrane topology" of a protein; i.e. predition of what parts of it protrude into the cell, what parts protrude out, and how many times the protein chain crosses the membrane. This information can be invaluable for developing antibodies, drugs or other reagents that will bind and/or affect the function of the protein.