(A) Global minimum energy conformation of cyclooxygenase 2 in the membrane. (B) Energy profiles obtained by pushing aligned proteins through the membrane. AQP, aquaporin from bovine red blood cell (1j4n); ClC, chloride channel homolog from E. coli (1kpk); SR, sensory rhodopsin (1h68); GpA, glycophorin A dimer (1afo, model 12); Cox 2, cyclooxygenase 2 (1cx2). The extracellular side is to the left. Except for Cox 2, all proteins can be seen to have a larger insertion penalty from the extracellular side, as well as a global insertion energy minimum at the membrane center. The insertion energy of Cox 2 is displayed on the y axis to the right, whereas all the other insertion energies are given on the left y axis.