The race to uncover new biological drug targets has led to an emerging field of research on the thermodynamic properties that stabilize transmembrane proteins as well as the role of these stabilizing factors in shaping the evolutionary landscape of drug target populations. When proteins are inserted into the plasma membrane, they fold into three- dimensional secondary protein structures called alpha helices. The electrical interactions within the alpha helix causes the protein to form a macrodipole. As a result of this phenomenon, the energetic stabilities of TM proteins may either be disrupted or enhanced due to the interactions between the surrounding membrane potential and the charged dipole termini of the folded helix. Currently, the relative contributions of compensatory factors to TM protein stability and their population distributions are poorly understood. In this study, two categories of bitopic proteins and the hydrophobic energies of their TM domains were investigated. We hypothesized that Type I TM proteins exhibit lower hydrophobic free energies as a compensatory response to the decreased electrical stabilities of Type I proteins that have incurred an energetic penalty due to the spatial orientations. A Z test showed that Type I proteins exhibit significantly lower hydrophobic free energies than Type II proteins (p = 0.0003, α = 0.05). A Z test of Shannon entropies of both protein types revealed that Type 1 proteins exhibit significantly lower Shannon entropies than those of Type 2 (p = 0.000, α = 0.05). Linear regression analysis showed a weak correlation between Type I Shannon entropies and Type I hydrophobic energies (R2 = 0.221) and Type II Shannon entropies and Type II hydrophobic energies (R2 = 0.232), suggesting that Shannon entropies are not a direct function of hydrophobic free energies and may arise from synergistic interactions among various energetic contributors.