Integral membrane proteins play important roles in living cells. Due to dif
ficulties of experimental techniques, theoretical approaches, i.e., topolog
y prediction methods, are important for structure determination of this cla
ss of proteins. Here we show a detailed comparison of transmembrane topolog
y prediction methods. According to this comparison, we conclude that the to
pology of integral membrane proteins is determined by the maximum divergenc
e of the amino acid composition of sequence segments. These segments are lo
cated in different areas of the cell, which can be characterized by differe
nt physicochemical properties. The results of these prediction methods comp
ared to the X-ray diffraction data of several transmembrane proteins will a
lso be discussed.